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Sample records for chronic murine typhoid

  1. Salmonella enterica serovar Typhimurium lacking hfq gene confers protective immunity against murine typhoid.

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    Uday Shankar Allam

    Full Text Available Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4(+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate.

  2. Expression and function of S100A8/A9 (calprotectin in human typhoid fever and the murine Salmonella model.

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    Hanna K De Jong

    2015-04-01

    Full Text Available Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8 and S100A9 (MRP14 form bioactive antimicrobial heterodimers (calprotectin that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model.S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury.S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response

  3. Typhoid fever

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    Wain, John; Hendriksen, Rene S.; Mikoleit, Matthew L.;

    2015-01-01

    Control of typhoid fever relies on clinical information, diagnosis, and an understanding for the epidemiology of the disease. Despite the breadth of work done so far, much is not known about the biology of this human-adapted bacterial pathogen and the complexity of the disease in endemic areas......, especially those in Africa. The main barriers to control are vaccines that are not immunogenic in very young children and the development of multidrug resistance, which threatens efficacy of antimicrobial chemotherapy. Clinicians, microbiologists, and epidemiologists worldwide need to be familiar...... with shifting trends in enteric fever. This knowledge is crucial, both to control the disease and to manage cases. Additionally, salmonella serovars that cause human infection can change over time and location. In areas of Asia, multidrug-resistant Salmonella enterica serovar Typhi (S Typhi) has been the main...

  4. Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

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    Ahn, Joong Hyun; Kim, Chi Hong; Kim, Yong Hyun; Kim, Seung Joon; Lee, Sook-Young; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak; Kwon, Soon Seog

    2007-01-01

    Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twen...

  5. Typhoid fever vaccination strategies.

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    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control.

  6. Typhoid fever in Ethiopia.

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    Beyene, Getenet; Asrat, Daniel; Mengistu, Yohannes; Aseffa, Abrham; Wain, John

    2008-12-01

    This review focuses on the reports of salmonellosis by investigators in different parts of Ethiopia, in particular focusing on the levels of typhoid fever. Many of the reports are published in local journals that are not available online. There have been seven studies which diagnosed typhoid fever by laboratory culture and there is no coordinated epidemiological surveillance. All conducted research and reports from different health institutions in Ethiopia indicate that typhoid fever was still a common problem up to the most recent study in 2000 and that the extensive use of first-line drugs has led to the development of multiple drug resistance. In the sites covered by this review, the total number of published cases of typhoid fever dropped over time reflecting the decline in research capacity in the country. Data on the proportion of patients infected by different serovars of Salmonella suggest that the non-Typhi serovars of Salmonella are increasing. The published evidence suggests that typhoid fever is a current public health problem in Ethiopia although population based surveys, based on good microbiological diagnosis, are urgently needed. Only then can the true burden of enteric fever be estimated and the benefit of public health control measures, such as health education, safe water provision, improved food hygienic practices and eventually vaccination, be properly assessed.

  7. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy

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    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24–48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  8. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy.

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    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24-48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  9. Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma

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    Jennifer Louten,; Mattson, Jeanine D.; Maria-Christina Malinao; Ying Li; Claire Emson; Felix Vega; Robert L. Wardle; Scott, Michael R.; Fick, Robert B.; McClanahan, Terrill K.; Rene de Waal Malefyt; Maribel Beaumont

    2012-01-01

    Background Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Objective Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. Methods The tot...

  10. Vaccines against typhoid fever.

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    Guzman, Carlos A; Borsutzky, Stefan; Griot-Wenk, Monika; Metcalfe, Ian C; Pearman, Jon; Collioud, Andre; Favre, Didier; Dietrich, Guido

    2006-05-01

    Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.

  11. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease

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    Dubovsky, Jason A.; Flynn, Ryan; Du, Jing; Harrington, Bonnie K.; Zhong, Yiming; Kaffenberger, Benjamin; Yang, Carrie; Towns, William H; Lehman, Amy; Johnson, Amy J.; Muthusamy, Natarajan; Devine, Steven M.; Jaglowski, Samantha; Serody, Jonathan S.; Murphy, William J.

    2014-01-01

    Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4+ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissi...

  12. Should close contacts of returning travellers with typhoid fever be protected by vaccination?

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    Kantele, A

    2015-03-17

    Increasing international travel to areas endemic for typhoid fever correlates with increased risk for travellers to contract the disease. At home, the acutely ill/convalescent patients may pose some risk to their close contacts. In Finland an unofficial guideline suggests vaccination for close contacts of patients with acute typhoid fever; in other developed countries, routine typhoid vaccinations are only recommended to contacts of chronic carriers. This paper discusses the possibilities and limitations of prophylactic/post-exposure typhoid vaccination for contacts of patients with acute disease.

  13. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

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    Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

    2011-08-01

    Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. PMID:21439399

  14. Typhoid Fever, Below the Belt.

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    Raveendran, Kamakshi Mahadevan; Viswanathan, Stalin

    2016-01-01

    Genital ulcers occur due to infective, inflammatory, malignant and drug-related causes. In tropical countries such as India, such ulcers are due to parasitic, tubercular, rickettsial and bacterial (sexually transmitted infections) aetiologies. Typhoid fever is endemic in the tropics. Except "rose spots", skin manifestations in typhoid fever are unusual, and they are missed due to pigmented skin. Patients do not often complain of genital ulcers due to shame or fear. Genital examination is not routinely performed in typhoid fever. We describe scrotal ulcers as the presenting symptom of typhoid fever, which subsided with appropriate therapy.

  15. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

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    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  16. Effectiveness of typhoid vaccination in US travelers.

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    Mahon, Barbara E; Newton, Anna E; Mintz, Eric D

    2014-06-17

    Typhoid vaccination is recommended in the United States before travel to countries where typhoid fever is endemic, though little information is available on its effectiveness in travelers. We estimated typhoid vaccination effectiveness (VE) by comparing vaccination status in cases of typhoid fever and paratyphoid fever (Salmonella Paratyphi A infection, against which typhoid vaccine offers no protection) reported in the United States. We included travelers to Southern Asia and excluded persons vaccination status was not reported. From 2008 through 2011, 744 eligible cases (602 typhoid, 142 paratyphoid A) were reported to CDC. Typhoid vaccination was reported for 5% (29/602) of typhoid patients and for 20% (29/142) of paratyphoid A patients. Estimated VE was 80% (95% confidence interval, 66-89%). Because of missing data, we could not estimate VE for specific vaccines. We demonstrated moderate effectiveness of typhoid vaccination in US travelers, supporting vaccination recommendations.

  17. Histological and In Vivo Microscopic Analysis of the Bone Marrow Microenvironment in a Murine Model of Chronic Myelogenous Leukemia.

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    Weissenberger, Eva S; Krause, Daniela S

    2016-01-01

    Imaging of the leukemic bone marrow microenvironment, also called the leukemic bone marrow niche, is an essential method to determine and to evaluate the progression of chronic myelogenous leukemia (CML) and other leukemias in murine models. In this chapter we introduce the murine model of CML primarily used in our laboratory by describing blood and bone marrow analysis as well as the method of histological sectioning and immunohistochemistry in combination with various stainings that can help to understand the complex interaction between leukemic cells, their normal hematopoietic counterparts, and the bone marrow microenvironment. We conclude with describing how to image the bone marrow niche using in vivo microscopy. PMID:27581139

  18. Specific probiotic dietary supplementation leads to different effects during remission and relapse in murine chronic colitis.

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    Zheng, B; van Bergenhenegouwen, J; van de Kant, H J G; Folkerts, G; Garssen, J; Vos, A P; Morgan, M E; Kraneveld, A D

    2016-01-01

    Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the effects of specific probiotic strains still remain unclear. Here, we assess the therapeutic effects of two probiotic strains, Lactobacillus rhamnosus NutRes 1 and Bifidobacterium breve NutRes 204 on a dextran sodium sulphate (DSS)-induced chronic murine colitis model. The chronic colitis was induced by two DSS treatment cycles with a rest period of 10 days (the remission or resolution phase). The probiotic supplementation was started during the resolution phase, after the first DSS treatment cycle, and continued until the end of the experiment. In addition to clinical observations made during the experiment, cellular infiltration was measured along with mRNA expression of pro-inflammatory cytokines, T cell-associated cytokines, and Toll like receptors (TLR) in the inflamed colon after second DSS treatment cycle. L. rhamnosus, but not B. breve, rapidly and effectively improved the DSS-induced bloody diarrhoea during the resolution phase. However, a contradictory effect by both probiotic strains on the faecal condition was found after re-induction of colitis. The worsening of the faecal condition was accompanied by a reduced number of neutrophils and increased expression of interferon-γ in the colons of DSS-treated mice. Furthermore, an increased expression of TLR2, TLR6 and pro-inflammatory markers including chemokine (C-C motif) ligand 2, interleukin (IL)-1β, tumour necrosis factor α and IL-6 was found in DSS-treated mice with L. rhamnosus supplementation. These results indicate that therapeutic administration of specific probiotics might be beneficial during the resolution phase of colitis. However, caution should be taken as specific probiotic treatments reduce neutrophil influx, which may be the reason of exacerbation of chronic colitis. PMID:26645352

  19. Predicting the impact of vaccination on the transmission dynamics of typhoid in South Asia: a mathematical modeling study.

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    Virginia E Pitzer

    Full Text Available BACKGROUND: Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed. METHODOLOGY/PRINCIPAL FINDINGS: We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000-2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R 0 of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively typhoid incidence was predicted to rebound 5-15 years following a one-time campaign. CONCLUSIONS/SIGNIFICANCE: We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone.

  20. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

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    Bonfield, Tracey L; Koloze, Mary; Lennon, Donald P; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I

    2010-12-01

    Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

  1. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

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    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  2. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

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    Ferrer, María F; Scharrig, Emilia; Alberdi, Lucrecia; Cedola, Maia; Pretre, Gabriela; Drut, Ricardo; Song, Wen-Chao; Gomez, Ricardo M

    2014-01-01

    Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  3. Excisional wound healing is delayed in a murine model of chronic kidney disease.

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    Akhil K Seth

    Full Text Available BACKGROUND: Approximately 15% of the United States population suffers from chronic kidney disease (CKD, often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment. METHODS: CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR. RESULTS: CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU and angiogenesis (CD31, with a concurrent increase in inflammation (CD45 as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS on qPCR. CONCLUSIONS: These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.

  4. A plasminogen activator inhibitor-1 inhibitor reduces airway remodeling in a murine model of chronic asthma.

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    Lee, Sun H; Eren, Mesut; Vaughan, Douglas E; Schleimer, Robert P; Cho, Seong H

    2012-06-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  5. [Typhoid fever in Chile 1977-1990: an emergent disease].

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    Cabello, F; Springer, A D

    1997-04-01

    The emergence of old and new communicable diseases is becoming an important public health problem in industrialized and developing countries worldwide. Chile experienced, at the end of the seventies and during the eighties, epidemics of several emergent communicable infectious diseases whose relevance as public health problems had steadily decreased in the previous 25 years. The most striking of these epidemics was a severe outbreak of typhoid fever that lasted at least 10 years. The majority of the cases occurred in the urban setting of Santiago. Several investigators suggested, in light of apparently good sanitation statistics, that factors responsible for this outbreak of typhoid were an increase in the number of chronic carriers of Salmonella typhi, the lack of microbiological food controls and the consumption of vegetables irrigated with waste water contaminated with S typhi. However, there is a dearth of epidemiological information and field work confirming the role of these factors in this typhoid outbreak. Moreover, the sudden, massive and urban characteristics of this epidemic, coupled to contemporary information regarding shortcomings on the preparation of drinking water and on decreased availability of drinking water to the population in Santiago regardless of good sanitation statistics, suggest that this outbreak may have been partially waterborne. The beginning of this typhoid outbreak also coincided with increased rain fall, with rapidly deteriorating economic and social conditions manifested in high rates of unemployment, and with decreased government investment on social services, including sanitation and health. All these factors are known to influence the epidemiology of typhoid and other emergent diseases worldwide. PMID:9460291

  6. Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications

    Directory of Open Access Journals (Sweden)

    C.J. Uneke

    2008-05-01

    Full Text Available Background & objectives: Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987–2007, to highlight the diagnostic challenges and the public health implications. Methods: Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Results: Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. Interpretation & conclusion: There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

  7. Analgesic effects of intra-articular botulinum toxin Type B in a murine model of chronic degenerative knee arthritis pain

    Directory of Open Access Journals (Sweden)

    Stephanie Anderson

    2010-09-01

    Full Text Available Stephanie Anderson1,2, Hollis Krug1,2, Christopher Dorman1, Pari McGarraugh1, Sandra Frizelle1, Maren Mahowald1,21Rheumatology Section, Veteran’s Affairs Medical Center, Minneapolis, Minnesota; 2Division of Rheumatology and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, Minnesota, USAObjective: To evaluate the analgesic effectiveness of intra-articular botulinum toxin Type B (BoNT/B in a murine model of chronic degenerative arthritis pain.Methods and materials: Chronic arthritis was produced in adult C57Bl6 mice by intra-articular injection of Type IV collagenase into the left knee. Following induction of arthritis, the treatment group received intra-articular BoNT/B. Arthritic control groups were treated with intra-articular normal saline or sham injections. Pain behavior testing was performed prior to arthritis, after induction of arthritis, and following treatments. Pain behavior measures included analysis of gait impairment (spontaneous pain behavior and joint tenderness evaluation (evoked pain response. Strength was measured as ability to grasp and cling.Results: Visual gait analysis showed significant impairment of gait in arthritic mice that improved 43% after intra-articular BoNT/B, demonstrating a substantial articular analgesic effect. Joint tenderness, measured with evoked pain response scores, increased with arthritis induction and decreased 49.5% after intra-articular BoNT/B treatment. No improvement in visual gait scores or decrease in evoked pain response scores were found in the control groups receiving intra-articular normal saline or sham injections. Intra-articular BoNT/B was safe, and no systemic effects or limb weakness was noted.Conclusions: This study is the first report of intra-articular BoNT/B for analgesia in a murine model of arthritis pain. The results of this study validate prior work using intra-articular neurotoxins in murine models. Our findings show chronic degenerative arthritis

  8. Formative investigation of acceptability of typhoid vaccine during a typhoid fever outbreak in Neno District, Malawi.

    Science.gov (United States)

    Blum, Lauren S; Dentz, Holly; Chingoli, Felix; Chilima, Benson; Warne, Thomas; Lee, Carla; Hyde, Terri; Gindler, Jacqueline; Sejvar, James; Mintz, Eric D

    2014-10-01

    Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to "bad wind," and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak.

  9. Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease

    OpenAIRE

    Aslam, Muhammad; Baveja, Rajiv; Liang, Olin D.; Fernandez-Gonzalez, Angeles; Lee, Changjin; Mitsialis, S. Alex; Kourembanas, Stella

    2009-01-01

    Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants.

  10. The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection.

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    Lisa Del Bel Belluz

    2016-04-01

    Full Text Available Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium strains, encoding either a functional or an inactive typhoid toxin. The presence of the genotoxic subunit was detected 10 days post-infection in the liver of infected mice. Unexpectedly, its expression promoted the survival of the host, and was associated with a significant reduction of severe enteritis in the early phases of infection. Immunohistochemical and transcriptomic analysis confirmed the toxin-mediated suppression of the intestinal inflammatory response. The presence of a functional typhoid toxin further induced an increased frequency of asymptomatic carriers. Our data indicate that the typhoid toxin DNA damaging activity increases host survival and favours long-term colonization, highlighting a complex cross-talk between infection, DNA damage response and host immune response. These findings may contribute to understand why such effectors have been evolutionary conserved and horizontally transferred among Gram-negative bacteria.

  11. Travelers' Health: Typhoid and Paratyphoid Fever

    Science.gov (United States)

    ... Visiting Friends and Family in Areas with Chikungunya, Dengue, or Zika Travel to the Olympics Infographic: Olympic ... water precautions and frequent handwashing are important in preventing typhoid and paratyphoid fever (see Chapter 2, Food & ...

  12. Molecular changes associated with chronic liver damage and neoplastic lesions in a murine model of hereditary tyrosinemia type 1.

    Science.gov (United States)

    Angileri, Francesca; Roy, Vincent; Morrow, Geneviève; Scoazec, Jean Yves; Gadot, Nicolas; Orejuela, Diana; Tanguay, Robert M

    2015-12-01

    Hereditary tyrosinemia type 1 (HT1) is the most severe inherited metabolic disease of the tyrosine catabolic pathway, with a progressive hepatic and renal injury and a fatal outcome if untreated. Toxic metabolites accumulating in HT1 have been shown to elicit endoplasmic reticulum (ER) stress response, and to induce chromosomal instability, cell cycle arrest and apoptosis perturbation. Although many studies have concentrated on elucidating these events, the molecular pathways responsible for development of hepatocellular carcinoma (HCC) still remain unclear. In this study the fah knockout murine model (fah(-/-)) was used to investigate the cellular signaling implicated in the pathogenesis of HT1. Fah(-/-) mice were subjected to drug therapy discontinuation (Nitisinone withdrawal), and livers were analyzed at different stages of the disease. Monitoring of mice revealed an increasing degeneration of the overall physiological conditions following drug withdrawal. Histological analysis unveiled diffuse hepatocellular damage, steatosis, oval-like cells proliferation and development of liver cell adenomas. Immunoblotting results revealed a progressive and chronic activation of stress pathways related to cell survival and proliferation, including several stress regulators such as Nrf2, eIF2α, CHOP, HO-1, and some members of the MAPK signaling cascade. Impairment of stress defensive mechanisms was also shown by microarray analysis in fah(-/-) mice following prolonged therapy interruption. These results suggest that a sustained activation of stress pathways in the chronic HT1 progression might play a central role in exacerbating liver degeneration. PMID:26360553

  13. Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

    OpenAIRE

    Nguyen, Long P.; Omoluabi, Ozozoma; Parra, Sergio; Frieske, Joanna M.; Clement, Cecilia; Ammar-Aouchiche, Zoulikha; Ho, Samuel B.; Ehre, Camille; Kesimer, Mehmet; Knoll, Brian J.; Tuvim, Michael J; Dickey, Burton F.; Bond, Richard A.

    2007-01-01

    Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers de...

  14. Building the case for wider use of typhoid vaccines.

    Science.gov (United States)

    Crump, John A

    2015-06-19

    Efficacious typhoid fever vaccines have been available for decades. Typhoid fever burden of disease estimates indicate a substantial burden of illness and death in low-resource areas. The World Health Organization has recommended that countries consider the use of typhoid vaccines for high-risk groups and populations, and for outbreak control. Despite this, typhoid vaccines are not widely used in endemic areas. By examining strategies to improve burden of disease data, use of transmission dynamic models, economic evaluations, vaccine strategies, and experiences with typhoid vaccine pilot projects, the papers in this supplement help to plot the path toward rational and wider use of typhoid vaccines.

  15. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Chen, Pei-Fen; Luo, Ya-ling; Wang, Wei; Wang, Jiang-xin; Lai, Wen-yan; Hu, Si-ming; Cheng, Kai Fan; Al-Abed, Yousef

    2010-01-01

    Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening, and airway wall area increase, similar to pathologies observed in human asthma. We used OVA-sensitized/challenged mice as a murine model of chronic allergic airway inflammation with subepithelial fibrosis (i.e., asthma). In this OVA mouse model, mRNA and protein of macrophage migration inhibitory factor (MIF) are upregulated, a response similar to what has been observed in the pathogenesis of acute inflammation in human asthma. We hypothesized that MIF induces transforming growth factor-β1 (TGF-β1) synthesis, which has been shown to play an important role in asthma and airway remodeling. To explore the role of MIF in the development of airway remodeling, we evaluated the effects of an MIF small-molecule antagonist, (S,R)3-(4-hy-droxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), on pathologies associated with the airway-remodeling process in the OVA mouse model. We found that administration of ISO-1 significantly mitigated all symptoms caused by OVA treatment. In addition, the treatment of OVA-sensitized mice with the MIF antagonist ISO-1 significantly reduced TGF-β1 mRNA levels in pulmonary tissue and its protein level in bronchial alveolar lavage fluid supernatants. We believe the repression of MIF in the ISO-1 treatment group led to the significant suppression observed in the inflammatory responses associated with the allergen-induced lung inflammation and fibrosis in our murine asthma (OVA) model. Our results implicate a

  16. Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

    Science.gov (United States)

    Cruz-Martinez, P; González-Granero, S; Molina-Navarro, M M; Pacheco-Torres, J; García-Verdugo, J M; Geijo-Barrientos, E; Jones, J; Martinez, S

    2016-01-01

    Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination. PMID:27171265

  17. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  18. Differential Contribution of Acute and Chronic Inflammation to the Development of Murine Mammary 4T1 Tumors.

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    Celso Tarso Rodrigues Viana

    Full Text Available Based on the notion that inflammation favors tumorigenesis, our experiments comparatively assessed the influence of acute and chronic inflammation on the development of a murine mammary tumor (4T1. In addition, we characterized angiogenic and inflammatory markers in the tumor tissue and systemically. Subcutaneous implantation of polyether-polyurethane sponge discs in Balb/c mice was used to host 4T1 tumor cells (1x10(6, which were inoculated intraimplant 24 h or 10 days post implantation. Flow cytometric analysis of enzyme-digested implants revealed that, after 24 hours, the population of leukocytes was primarily characterized by neutrophils (42.53% +/- 8.45 and monocytes (37.53% +/- 7.48, with some lymphocytes (16.27% +/- 4.0 and a few dendritic cells (1.82% +/- 0.36. At 10 days, macrophages were predominant (37.10% +/- 4.54, followed by lymphocytes (28.1% +/- 4.77, and monocytes (22.33% +/- 3.05, with some dendritic cells (13.60% +/- 0.55 and neutrophils (11.07% +/- 2.27. A mammary tumor grown in a chronic inflammatory environment was 2-fold when compared with one grown in acute inflammation and 5-fold when compared with tumor alone. The levels of pro-angiogenic cytokine (VEGF-Vascular Endothelial Growth Factor were higher in implant-bearing tumor when 4T1 cells were grown in 10-day old implants as compared to the VEGF levels of the two other groups. Overall, the levels of the inflammatory markers evaluated (NAG -N-acetylglucosaminidase, TNF-α-Tumor Necrosis Factor-α were higher in both groups of implant-bearing tumors and in serum from those animals when compared with the tumor alone levels. This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression.

  19. MALARIA TYPHOID CO - INFECTION AMONG FEBRILE PATIENTS

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    Samatha

    2015-08-01

    Full Text Available Malaria and typhoid fevers, caused by different organisms are major public health problems in developing countries. People in endemic areas are at risk of both infections concurrently. These are the important cause of fevers in many endemic areas especially during rainy season. Each of these diseases can substantially contribute to mortality if not diagnosed and treated early. The present study was designed to find the Sero prevalence of Malaria, Typhoid and Typho malarial co - infections in febrile patients. METHODS: A cross sectional study was conducted from June 2014 to May 2015. A total of five hundred and eighty two subjects were screened for Malaria and Typhoid is included in study irrespective of their age & sex. Data was analysed on the basis of Demographic factors & Serological results. The results were analysed statistically. RESULTS: The seroprevalence of malarial infection was found to be 58.41% , Typhoid as 1.8 % whereas, True Typho Malarial co - infection was seen in 0.7%. CONCLUSION: The present study reports the Prevalence of Malaria, Typhoid and Typho Malarial Co - infection which are important when planning large scale vaccine trials as well as making health policies and a Protocol is required to treat these infections to limit the mortality and morbidity.

  20. Differential effects of Smad3 targeting in a murine model of chronic kidney disease

    DEFF Research Database (Denmark)

    Kellenberger, Terese; Krag, Søren; Danielsen, Carl Christian;

    2013-01-01

    genes involved in extracellular matrix (ECM) metabolism. This study analyzes the hypothesis that blockade of Smad3 attenuates the development of TGF-β1-driven renal fibrosis. This was examined in vivo in a transgenic model of TGF-β1-induced chronic kidney disease with Smad3 or without Smad3 expression......Transforming growth factor (TGF)-β1 has a pivotal role in the pathogenesis of progressive kidney diseases that are characterized by fibrosis. The main intracellular signaling pathway of TGF-β1 is the Smad system, where Smad2 and Smad3 play a central role in transcriptional regulation of target...... in the kidney....

  1. Effect of diosmetin on airway remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Ge, Ai; Liu, Yanan; Zeng, Xiaoning; Kong, Hui; Ma, Yuan; Zhang, Jiaxiang; Bai, Fangfang; Huang, Mao

    2015-08-01

    Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. The anti-oxidant flavone aglycone diosmetin ameliorates the inflammation in pancreatitis, but little is known about its impact on asthma. In this study, the effects of diosmetin on chronic asthma were investigated with an emphasis on the modulation of airway remodeling in BALB/c mice challenged with ovalbumin (OVA). It was found that diosmetin significantly relieved inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in the lungs of asthmatic mice and notably reduced AHR in these animals. The OVA-induced increases in total cell and eosinophil counts in bronchoalveolar lavage fluid were reversed, and the level of OVA-specific immunoglobulin E in serum was attenuated by diosmetin administration, implying an anti-Th2 activity of diosmetin. Furthermore, diosmetin remarkably suppressed the expression of smooth muscle actin alpha chain, indicating a potent anti-proliferative effect of diosmetin on airway smooth muscle cells (ASMCs). Matrix metallopeptidase-9, transforming growth factor-β1, and vascular endothelial growth factor levels were also alleviated by diosmetin, suggesting that the remission of airway remodeling might be attributed to the decline of these proteins. Taken together, our findings provided a novel profile of diosmetin with anti-remodeling therapeutic benefits, highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma. PMID:26033789

  2. Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease.

    Science.gov (United States)

    Fox, Christopher; Cocchiaro, Pasquale; Oakley, Fiona; Howarth, Rachel; Callaghan, Krystena; Leslie, Jack; Luli, Saimir; Wood, Katrina M; Genovese, Federica; Sheerin, Neil S; Moles, Anna

    2016-01-01

    During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for cathepsins in CKD. CtsD and B were located in distal and proximal tubular cells respectively in human disease. Administration of CtsD (Pepstatin A) but not B inhibitor (Ca074-Me), in two mouse CKD models, UUO and chronic ischemia reperfusion injury, led to a reduction in fibrosis. No changes in collagen transcription or myofibroblasts numbers were observed. Pepstatin A administration resulted in increased extracellular urokinase and collagen degradation. In vitro and in vivo administration of chloroquine, an endo/lysosomal inhibitor, mimicked Pepstatin A effect on renal fibrosis. Therefore, we propose a mechanism by which CtsD inhibition leads to increased collagenolytic activity due to an impairment in lysosomal recycling. This results in increased extracellular activity of enzymes such as urokinase, triggering a proteolytic cascade, which culminates in more ECM degradation. Taken together these results suggest that inhibition of lysosomal proteases, such as CtsD, could be a new therapeutic approach to reduce renal fibrosis and slow progression of CKD. PMID:26831567

  3. Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis.

    Directory of Open Access Journals (Sweden)

    Benyam P Yoseph

    Full Text Available BACKGROUND: Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. METHODS: Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. RESULTS: Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01. This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. CONCLUSIONS: When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality

  4. Optical coherence tomography (OCT) of a murine model of chronic kidney disease

    Science.gov (United States)

    Wang, Hsing-Wen; Guo, Hengchang; Andrews, Peter M.; Anderson, Erik; Chen, Y.

    2015-03-01

    Chronic Kidney Disease (CKD) is characterized by a progressive loss in renal function over time. Pathology can provide valuable insights into the progression of CKD by analyzing the status of glomeruli and the uriniferous tubules over time. Optical coherence tomography (OCT) is a new procedure that can analyze the microscopic structure of the kidney in a non-invasive manner. This is especially important because there are significant artifacts associated with excision biopsies and immersion fixation procedures. Recently, we have shown that OCT can provide real time images of kidney microstructure and Doppler OCT (DOCT) can image glomerular renal blood flow in vivo without administrating exogenous contrast agents. In this study, we used OCT to evaluate CKD in a model induced by intravenous Adriamycin injection into Munich-Wistar rats. We evaluated tubular density and tubular diameter from OCT images at several post- Adriamycin induction time points and compared them with conventional light microscopic histological imaging. Proteinurea and serum creatinine were used as physiological markers of the extent of CKD. Preliminary OCT results revealed changes in tubular density due to tubular necrosis and interstitial fibrosis within the first 4 weeks following Adriamycin injection. From week 4 to 8 after Adriamycin induction, changes in tubular density and diameter occurred due to both tubular loss and tubular dilation. The results suggest OCT can provide additional information about kidney histopathology in CKD. DOCT revealed reduced blood flow in some glomeruli probably as a consequence of focal glomerularsclerosis.

  5. Blockade of CCR2 reduces macrophage influx and development of chronic renal damage in murine renovascular hypertension.

    Science.gov (United States)

    Kashyap, Sonu; Warner, Gina M; Hartono, Stella P; Boyilla, Rajendra; Knudsen, Bruce E; Zubair, Adeel S; Lien, Karen; Nath, Karl A; Textor, Stephen C; Lerman, Lilach O; Grande, Joseph P

    2016-03-01

    Renovascular hypertension (RVH) is a common cause of both cardiovascular and renal morbidity and mortality. In renal artery stenosis (RAS), atrophy in the stenotic kidney is associated with an influx of macrophages and other mononuclear cells. We tested the hypothesis that chemokine receptor 2 (CCR2) inhibition would reduce chronic renal injury by reducing macrophage influx in the stenotic kidney of mice with RAS. We employed a well-established murine model of RVH to define the relationship between macrophage infiltration and development of renal atrophy in the stenotic kidney. To determine the role of chemokine ligand 2 (CCL2)/CCR2 signaling in the development of renal atrophy, mice were treated with the CCR2 inhibitor RS-102895 at the time of RAS surgery and followed for 4 wk. Renal tubular epithelial cells expressed CCL2 by 3 days following surgery, a time at which no significant light microscopic alterations, including interstitial inflammation, were identified. Macrophage influx increased with time following surgery. At 4 wk, the development of severe renal atrophy was accompanied by an influx of inducible nitric oxide synthase (iNOS)+ and CD206+ macrophages that coexpressed F4/80, with a modest increase in macrophages coexpressing arginase 1 and F4/80. The CCR2 inhibitor RS-102895 attenuated renal atrophy and significantly reduced the number of dual-stained F4/80+ iNOS+ and F4/80+ CD206+ but not F4/80+ arginase 1+ macrophages. CCR2 inhibition reduces iNOS+ and CD206+ macrophage accumulation that coexpress F4/80 and renal atrophy in experimental renal artery stenosis. CCR2 blockade may provide a novel therapeutic approach to humans with RVH.

  6. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    H.S. Campos

    2006-02-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  7. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    Campos H.S.

    2006-01-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  8. New generation typhoid vaccines: an effective preventive strategy to control typhoid fever in developing countries.

    Science.gov (United States)

    Verma, Ramesh; Bairwa, Mohan; Chawla, Suraj; Prinja, Shankar; Rajput, Meena

    2011-08-01

    Typhoid fever is a serious systemic infection, caused by the enteric pathogen Salmonella enterica serovar Typhi, a highly virulent and invasive enteric bacterium. This disease occurs in all parts of world where water supplies and sanitation are substandard. These pathogens then travel to food, drinks and water through house-flies and other vectors. Globally, an estimated 12-33 million cases of enteric fever occur with 216,00-600,000 deaths per year, almost exclusively in the developing countries. Health surveys conducted by the Health Ministry of India in the community development areas indicated a morbidity rate varying from 102-2219/100,000 population in different parts of the country. A limited study in an urban slum showed 1% of children up to 17 years of age suffer from typhoid fever annually. The continued high burden of typhoid fever and the alarming spread of antibiotic resistant strains led the World Health Organization (WHO), almost ten years ago, to recommend immunization using the two new-generation vaccines in school- aged children in areas where typhoid fever posed a significant problem and where antibiotic resistant strains were prevalent. Morbidity and mortality due to high incidence of typhoid fever favors the introduction of typhoid vaccine in routine immunization in India. This vaccine should be given at the age of 2 years with Vi antigen vaccine and at least one more dose be given at 5 years of age.

  9. Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis

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    van Bodegraven Adriaan A

    2011-05-01

    Full Text Available Abstract Background Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG and azathioprine (AZA in a murine model of IBD. Methods We induced acute or chronic colitis in BALB/c mice by one or four cycles of 3% dextran sulphate sodium (DSS, respectively. Mice were treated by daily gavages of various dosages of 6-tioguanine, azathioprine, or by phosphate buffered saline (PBS starting the first day of DSS or after two cycles of DSS, respectively. We monitored the efficacy and toxicity by measuring the weight change and serum alanine aminotransferase (ALT activity and by disease severity and histology, at the end of the experiment. Moreover, we measured cytokine production after colon fragment cultivation by enzyme-linked immunoabsorbent assay and numbers of apoptotic cells in the spleen by flow cytometry. Results 6-TG is effective in the treatment of acute DSS-induced colitis in a dose-dependent manner and 40 μg of 6-TG is significantly more effective in the treatment of acute colitis than both AZA and PBS. This effect is accompanied by decrease of IL-6 and IFN-γ production in colon. We did not observe histological abnormalities in liver samples from control (PBS or 6-TG treated mice. However, liver samples from most mice treated with AZA showed mild, yet distinct signs of hepatotoxicity. In chronic colitis, all thiopurine derivatives improved colitis, 20 μg of 6-TG per dose was superior. High doses of 6-TG led to significant weight loss at the end of the therapy, but none of the thiopurine derivatives increased levels of serum ALT. Both thiopurine derivatives reduced the proportion of apoptotic T helper cells, but a high production of both IL-6 and TGF-β was observed only in colon of AZA-treated mice. Conclusions Use of 6-TG in the treatment

  10. Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.

    Science.gov (United States)

    Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A; Sun, Ying; Pan, Dao

    2016-01-01

    To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD. PMID:27598339

  11. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

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    Adamcakova-Dodd Andrea

    2012-06-01

    Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

  12. Identification of carriers among individuals recruited in the typhoid registry in Malaysia using stool culture, polymerase chain reaction, and dot enzyme immunoassay as detection tools.

    Science.gov (United States)

    Chua, Ang Lim; Aziah, Ismail; Balaram, Prabha; Bhuvanendran, Saatheeyavaane; Anthony, Amy Amilda; Mohmad, Siti Norazura; Nasir, Norhafiza M; Hassan, Haslizai; Naim, Rochman; Meran, Lila P; Hussin, Hani M; Ismail, Asma

    2015-03-01

    Chronic carriers of Salmonella Typhi act as reservoirs for the organism and become the agents of typhoid outbreaks in a community. In this study, chronic carriers in Kelantan, Malaysia were first identified using the culture and polymerase chain reaction method. Then, a novel serological tool, designated Typhidot-C, was evaluated in retrospect using the detected individuals as control positives. Chronic carriage positive by the culture and polymerase chain reaction method was recorded at 3.6% (4 out of 110) among individuals who previously had acute typhoid fever and a 9.4% (10 out of 106) carriage rate was observed among food handlers screened during outbreaks. The Typhidot-C assay was able to detect all these positive carriers showing its potential as a viable carrier screening tool and can be used for efficient detection of typhoid carriers in an endemic area. These findings were used to establish the first carrier registry for S Typhi carriers in Malaysia. PMID:23000800

  13. Mycobacterial Bacilli Are Metabolically Active during Chronic Tuberculosis in Murine Lungs: Insights from Genome-Wide Transcriptional Profiling

    Science.gov (United States)

    Chronic tuberculosis represents a major health problem for one third of the world’s population today. A key question relevant to chronic tuberculosis is the physiological status of Mycobacterium tuberculosis during this important stage of infection. Previous work on chronic tuberculosis revealed t...

  14. Typhoid fever : aspects of environment, host and pathogen interaction

    NARCIS (Netherlands)

    Ali, Soegianto

    2006-01-01

    In a surveillance study in Jakarta, Indonesia, 88 typhoid and 26 paratyphoid fever patients were identified by blood culture. Risk factors for transmission of typhoid fever were mainly intra-household factors (poor hand-washing hygiene, recent household contacts), whereas paratyphoid was mainly cont

  15. 25 years after Vi typhoid vaccine efficacy study, typhoid affects significant number of population in Nepal.

    Directory of Open Access Journals (Sweden)

    Deepak Bajracharya

    Full Text Available Salmonella Typhi, first isolated in 1884, results in infection of the intestines and can end in death and disability. Due to serious adverse events post vaccination, whole cell killed vaccines have been replaced with new generation vaccines. The efficacy of Vi polysaccharide (ViPS vaccine, a new generation, single-dose intramuscular typhoid vaccine was assessed in Nepal in 1987. However, despite the availability of ViPS vaccine for more than 25 years, Nepal has one of the highest incidence of typhoid fever. Therefore we collected information from hospitals in the Kathmandu Valley from over the past five years. There were 9901 enteric fever cases between January 2008 and July 2012. 1,881 of these were confirmed typhoid cases from five hospitals in the Kathmandu district. Approximately 70% of the cases involved children under 15 years old. 1281 cases were confirmed as S. Paratyphi. Vaccines should be prioritized for control of typhoid in conjunction with improved water and sanitation conditions in Nepal and in endemic countries of Asia and Africa.

  16. 25 years after Vi typhoid vaccine efficacy study, typhoid affects significant number of population in Nepal.

    Science.gov (United States)

    Bajracharya, Deepak; Khan, M Imran; Pach, Alfred; Shrestha, Parisha; Joshi, Nilesh; Upreti, Shyam R; Wierzba, Thomas; Puri, Mahesh; Sahastrabuddhe, Sushant; Ochiai, R Leon

    2014-01-01

    Salmonella Typhi, first isolated in 1884, results in infection of the intestines and can end in death and disability. Due to serious adverse events post vaccination, whole cell killed vaccines have been replaced with new generation vaccines. The efficacy of Vi polysaccharide (ViPS) vaccine, a new generation, single-dose intramuscular typhoid vaccine was assessed in Nepal in 1987. However, despite the availability of ViPS vaccine for more than 25 years, Nepal has one of the highest incidence of typhoid fever. Therefore we collected information from hospitals in the Kathmandu Valley from over the past five years. There were 9901 enteric fever cases between January 2008 and July 2012. 1,881 of these were confirmed typhoid cases from five hospitals in the Kathmandu district. Approximately 70% of the cases involved children under 15 years old. 1281 cases were confirmed as S. Paratyphi. Vaccines should be prioritized for control of typhoid in conjunction with improved water and sanitation conditions in Nepal and in endemic countries of Asia and Africa.

  17. Typhoid transmission: a historical perspective on mathematical model development.

    Science.gov (United States)

    Bakach, Iurii; Just, Matthew R; Gambhir, Manoj; Fung, Isaac Chun-Hai

    2015-11-01

    Mathematical models of typhoid transmission were first developed nearly half a century ago. To facilitate a better understanding of the historical development of this field, we reviewed mathematical models of typhoid and summarized their structures and limitations. Eleven models, published in 1971 to 2014, were reviewed. While models of typhoid vaccination are well developed, we highlight the need to better incorporate water, sanitation and hygiene interventions into models of typhoid and other foodborne and waterborne diseases. Mathematical modeling is a powerful tool to test and compare different intervention strategies which is important in the world of limited resources. By working collaboratively, epidemiologists and mathematicians should build better mathematical models of typhoid transmission, including pharmaceutical and non-pharmaceutical interventions, which will be useful in epidemiological and public health practice.

  18. Typhoid fever & vaccine development: a partially answered question.

    Science.gov (United States)

    Marathe, Sandhya A; Lahiri, Amit; Negi, Vidya Devi; Chakravortty, Dipshikha

    2012-01-01

    Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S. Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

  19. Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Christine Breynaert

    Full Text Available INTRODUCTION: Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS ingestion, to mimic the relapsing nature of the human disease. MATERIALS AND METHODS: C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total. Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. RESULTS: Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn's colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. CONCLUSIONS: Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn's disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of

  20. Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model.

    Science.gov (United States)

    Wei, Ying; Liu, Baojun; Sun, Jing; Lv, Yubao; Luo, Qingli; Liu, Feng; Dong, Jingcheng

    2015-06-01

    Icariin which is a flavonoid glucoside isolated from Epimedium brevicornu Maxim, has been reported to have anti-osteoporotic, anti-inflammatory and anti-depressant-like activities. In this study, we observed the effect of icariin on airway inflammation of ovalbumin (OVA)-induced murine asthma model and the associated regulatory mode on T-helper (Th)17 and regulatory T (Treg) cell function. Our data revealed that chronic OVA inhalation induced a dramatic increase in airway resistance (RL) and decrease in the lung dynamic compliance (Cdyn), and icariin and DEX treatment caused significant attenuation of such airway hyperresponsiveness (AHR). BALF cell counts demonstrated that icariin and DEX led to a prominent reduction in total leukocyte as well as lymphocyte, eosinophil, neutrophil, basophil and monocyte counts. Histological analysis results indicated that icariin and DEX alleviated the inflammatory cells infiltrating into the peribronchial tissues and goblet cells hyperplasia and mucus hyper-production. Flow cytometry test demonstrated that icariin or DEX administration resulted in a significant percentage reduction in CD4+RORγt+ T cells and elevation of CD4+Foxp3+ T cells in BALF. Furthermore, icariin or DEX caused a significant reduction in IL-6, IL-17 and TGF-β level in BALF. Unfortunately, icariin had no effect on IL-10 level in BALF. Western blot assay found that icariin or DEX suppressed RORγt and promoted Foxp3 expression in the lung tissue. qPCR analysis revealed that icariin and DEX resulted in a notable decrease in RORγt and increase in Foxp3 mRNA expression in isolated spleen CD4+ T cell. In conclusion, our results suggested that icariin was effective in the attenuation of AHR and chronic airway inflammatory changes in OVA-induced murine asthma model, and this effect was associated with regulation of Th17/Treg responses, which indicated that icariin may be used as a potential therapeutic method to treat asthma with Th17/Treg imbalance phenotype

  1. Assessing the Cytotoxicity of Black Carbon As A Model for Ultrafine Anthropogenic Aerosol Across Human and Murine Cells: A Chronic Exposure Model of Nanosized Particulate Matter

    Science.gov (United States)

    Salinas, E.

    2015-12-01

    Combustion-derived nanomaterials or ultrafine (Juarez, Chihuahua, Mexico, comprising the Paso del Norte air basin. A study conducted by scientists from the Research Triangle Park in North Carolina, analyzed sites adjacent to heavy-traffic highways in El Paso and elucidated higher UFP concentrations in comparison to previously published work exploring pollution and adverse health effects in the basin. UFPs can penetrate deep into the alveolar sacs of the lung, reaching distant alveolar sacs and inducing a series of immune responses that are detrimental to the body: evidence suggests that UFPs can also cross the alveolar-blood barrier and potentially endanger the body's immune response. The physical properties of UFPs and the dynamics of local atmospheric and topographical conditions indicate that emissions of nanosized carbonaceous aerosols could pose significant threats to biological tissues upon inhalation by local residents of the Paso del Norte. This study utilizes Black Carbon (BC) as a model for environmental UFPs and its effects on the immunological response. An in vitro approach is used to measure the ability of BC to promote cell death upon long-term exposure. Human epithelial lung cells (A549), human peripheral-blood monocytes (THP-1), murine macrophages (RAW264.7), and murine epithelial lung cells (LA-4) were treated with BC and assessed for metabolic activity after chronic exposure utilizing three distinct and independent cell viability assays. The cell viability experiments included a chronic study at 7, 10, and 14 days of UFP exposure at six different concentrations of BC: 100μM, 300μM, 600μM, 1,250μM, 2,500μM, and 5,000μM conducting the Trypan Blue (TB) Exclusion Assay, Calcein-AM Viability Assay, and CellTiter-Glo Viability Assay.

  2. Cases of typhoid fever in Copenhagen region

    DEFF Research Database (Denmark)

    Barrett, Freja Cecille; Knudsen, Jenny Dahl; Johansen, Isik Somuncu

    2013-01-01

    Typhoid fever is a systemic illness which in high-income countries mainly affects travellers. The incidence is particularly high on the Indian subcontinent. Travellers who visit friends and relatives (VFR) have been shown to have a different risk profile than others. We wished to identify main ch...... characteristics for travellers infected with S. Typhi considering both clinical and laboratory findings in order to provide for faster and better diagnostics in the future. The outcome of treatment, especially concerning relapse, was evaluated as well....

  3. Murine gamma interferon fails to inhibit Toxoplasma gondii growth in murine fibroblasts.

    Science.gov (United States)

    Schwartzman, J D; Gonias, S L; Pfefferkorn, E R

    1990-01-01

    Although treatment of human macrophages or fibroblasts with human gamma interferon results in the inhibition of intracellular Toxoplasma gondii, murine gamma interferon stimulated only murine macrophages, not murine fibroblasts, to inhibit T. gondii. This species difference may be important in understanding the control of acute and chronic toxoplasmosis. PMID:2106497

  4. Axl tyrosine kinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia.

    Directory of Open Access Journals (Sweden)

    Gareth D Hyde

    Full Text Available Chronic kidney disease (CKD is defined as the progressive loss of renal function often involving glomerular, tubulo-interstitial and vascular pathology. CKD is associated with vascular calcification; the extent of which predicts morbidity and mortality. However, the molecular regulation of these events and the progression of chronic kidney disease are not fully elucidated. To investigate the function of Axl receptor tyrosine kinase in CKD we performed a sub-total nephrectomy and fed high phosphate (1% diet to Axl+/+ and Axl-/- mice. Plasma Gas6 (Axl' ligand, renal Axl expression and downstream Akt signalling were all significantly up-regulated in Axl+/+ mice following renal mass reduction and high phosphate diet, compared to age-matched controls. Axl-/- mice had significantly enhanced uraemia, reduced bodyweight and significantly reduced survival following sub-total nephrectomy and high phosphate diet compared to Axl+/+ mice; only 45% of Axl-/- mice survived to 14 weeks post-surgery compared to 87% of Axl+/+ mice. Histological analysis of kidney remnants revealed no effect of loss of Axl on glomerular hypertrophy, calcification or renal sclerosis but identified significantly increased tubulo-interstitial apoptosis in Axl-/- mice. Vascular calcification was not induced in Axl+/+ or Axl-/- mice in the time frame we were able to examine. In conclusion, we identify the up-regulation of Gas6/Axl signalling as a protective mechanism which reduces tubulo-interstitial apoptosis and slows progression to end-stage renal failure in the murine nephrectomy and high phosphate diet model of CKD.

  5. Axl tyrosine kinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia.

    Science.gov (United States)

    Hyde, Gareth D; Taylor, Rebecca F; Ashton, Nick; Borland, Samantha J; Wu, Hon Sing Geoffrey; Gilmore, Andrew P; Canfield, Ann E

    2014-01-01

    Chronic kidney disease (CKD) is defined as the progressive loss of renal function often involving glomerular, tubulo-interstitial and vascular pathology. CKD is associated with vascular calcification; the extent of which predicts morbidity and mortality. However, the molecular regulation of these events and the progression of chronic kidney disease are not fully elucidated. To investigate the function of Axl receptor tyrosine kinase in CKD we performed a sub-total nephrectomy and fed high phosphate (1%) diet to Axl+/+ and Axl-/- mice. Plasma Gas6 (Axl' ligand), renal Axl expression and downstream Akt signalling were all significantly up-regulated in Axl+/+ mice following renal mass reduction and high phosphate diet, compared to age-matched controls. Axl-/- mice had significantly enhanced uraemia, reduced bodyweight and significantly reduced survival following sub-total nephrectomy and high phosphate diet compared to Axl+/+ mice; only 45% of Axl-/- mice survived to 14 weeks post-surgery compared to 87% of Axl+/+ mice. Histological analysis of kidney remnants revealed no effect of loss of Axl on glomerular hypertrophy, calcification or renal sclerosis but identified significantly increased tubulo-interstitial apoptosis in Axl-/- mice. Vascular calcification was not induced in Axl+/+ or Axl-/- mice in the time frame we were able to examine. In conclusion, we identify the up-regulation of Gas6/Axl signalling as a protective mechanism which reduces tubulo-interstitial apoptosis and slows progression to end-stage renal failure in the murine nephrectomy and high phosphate diet model of CKD.

  6. A Case Report of Typhoidal Acute Acalculous Cholecystitis

    Directory of Open Access Journals (Sweden)

    Neeha Rajan

    2014-01-01

    Full Text Available Introduction. Acalculous cholecystitis in the setting of typhoid fever in adults is an infrequent clinical encounter, reported sparsely in the literature. In this case report we review the presentation and management of enteric fever involving the biliary system and consider the literature surrounding this topic. The aim of this case report is to alert clinicians to the potential diagnosis of extraintestinal complications in the setting of typhoid fever in the returned traveller, requiring surgical intervention. Presentation of Case. We report the case of a 23-year-old woman with acalculous cholecystitis secondary to Salmonella Typhi. Discussion. There is scarce evidence surrounding the optimal treatment and prognosis of typhoidal acalculous cholecystitis. In the current case, surgical invention was favoured due to failure of medical management. Conclusion. Clinical judgement dictated surgical intervention in this case of typhoidal acute acalculous cholecystitis, and cholecystectomy was safely performed.

  7. Typhoid vaccine: A case for inclusion in national program

    Directory of Open Access Journals (Sweden)

    Pragya Sharma

    2011-01-01

    Full Text Available Typhoid has been reported to be a common and significant cause of morbidity in pre-school and school-age children in the endemic countries like India. The incidence of typhoid has been reported to be as high as 27.3 per 1000 person-years in children less than 5 years of age. Serious complications occur in about 10% of cases requiring hospitalization. The mean cost of treatment per episode of blood culture-confirmed typhoid fever has been calculated as INR 3,597 (1996 prices in an outdoor setting, whereas in case of hospitalization, the cost of illness increases by several folds (INR 18,131. Vi polysaccharide vaccine is safe, efficacious and affordable for use as a cost-effective public health tool to protect children from typhoid and related complications, when given at 2 and 5 years of age as a part of National Immunization Schedule.

  8. Typhoid vaccine: a case for inclusion in national program.

    Science.gov (United States)

    Sharma, Pragya; Taneja, Davendra K

    2011-01-01

    Typhoid has been reported to be a common and significant cause of morbidity in pre-school and school-age children in the endemic countries like India. The incidence of typhoid has been reported to be as high as 27.3 per 1000 person-years in children less than 5 years of age. Serious complications occur in about 10% of cases requiring hospitalization. The mean cost of treatment per episode of blood culture-confirmed typhoid fever has been calculated as INR 3,597 (1996 prices) in an outdoor setting, whereas in case of hospitalization, the cost of illness increases by several folds (INR 18,131). Vi polysaccharide vaccine is safe, efficacious and affordable for use as a cost-effective public health tool to protect children from typhoid and related complications, when given at 2 and 5 years of age as a part of National Immunization Schedule.

  9. S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.

    Science.gov (United States)

    Yoon, Sun-Young; Hong, Gyong Hwa; Kwon, Hyouk-Soo; Park, Sunjoo; Park, So Young; Shin, Bomi; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2016-06-03

    Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.

  10. Vaccination for typhoid fever in Sub-Saharan Africa

    OpenAIRE

    Slayton, Rachel B.; Date, Kashmira A.; Eric D Mintz

    2013-01-01

    New data on the epidemiologic, clinical and microbiologic aspects of typhoid fever in sub-Saharan Africa call for new strategies and new resources to bring the regional epidemic under control. Areas with endemic disease at rates approaching those in south Asia have been identified; large, prolonged and severe outbreaks are occurring more frequently; and resistance to antimicrobial agents, including fluoroquinolones is increasing. Surveillance for typhoid fever is hampered by the lack of labor...

  11. Risk Factors of Typhoid Infection in the Indonesian Archipelago

    OpenAIRE

    Alba, Sandra; Bakker, Mirjam I; Hatta, Mochammad; Pauline F D Scheelbeek; Dwiyanti, Ressy; Usman, Romi; Sultan, Andi R.; Sabir, Muhammad; Tandirogang, Nataniel; Amir, Masyhudi; Yasir, Yadi; Pastoor, Rob; van Beers, Stella; Henk L. Smits

    2016-01-01

    Background Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua) in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas. Methods We enrolled 933 patients above 10 years of ...

  12. Seroincidence of non-typhoid Salmonella infections

    DEFF Research Database (Denmark)

    Emborg, H-D; Simonsen, J; Jørgensen, C S;

    2016-01-01

    The incidence of reported infections of non-typhoid Salmonella is affected by biases inherent to passive laboratory surveillance, whereas analysis of blood sera may provide a less biased alternative to estimate the force of Salmonella transmission in humans. We developed a mathematical model...... that enabled a back-calculation of the annual seroincidence of Salmonella based on measurements of specific antibodies. The aim of the present study was to determine the seroincidence in two convenience samples from 2012 (Danish blood donors, n = 500, and pregnant women, n = 637) and a community-based sample...... of healthy individuals from 2006 to 2007 (n = 1780). The lowest antibody levels were measured in the samples from the community cohort and the highest in pregnant women. The annual Salmonella seroincidences were 319 infections/1000 pregnant women [90% credibility interval (CrI) 210-441], 182/1000 in blood...

  13. Limitations of typhoid vaccination for travellers.

    Science.gov (United States)

    Stephen, J; Mara, N; Nathwani, D

    1996-12-01

    Around one-third of travellers to endemic areas receive pre-travel typhoid vaccination, increasingly with the new parenteral vaccination Typhim Vi (Mérieux). More than 200 cases of Salmonella typhi and S. paratyphi infection are imported into the UK each year. Despite the widespread use of immunisation, non-specialist clinicians and the travelling public do not appear to fully appreciate the limitations of currently available vaccination. These limitations are not adequately highlighted in either the Green Book of Immunisation against Infectious Diseases (HMSO, 1992) or the new handbook Health Information for Overseas Travel (HMSO, 1995) which are important sources of reference for clinicians and practice nurses. This may delay consideration of diagnosis and presentation for treatment in immunised travellers.

  14. Development of Vi conjugate - a new generation of typhoid vaccine.

    Science.gov (United States)

    Szu, Shousun Chen

    2013-11-01

    Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination.

  15. Vaccination for typhoid fever in sub-Saharan Africa.

    Science.gov (United States)

    Slayton, Rachel B; Date, Kashmira A; Mintz, Eric D

    2013-04-01

    Emerging data on the epidemiologic, clinical and microbiologic aspects of typhoid fever in sub-Saharan Africa call for new strategies and new resources to bring the regional epidemic under control. Areas with endemic disease at rates approaching those in south Asia have been identified; large, prolonged and severe outbreaks are occurring more frequently; and resistance to antimicrobial agents, including fluoroquinolones is increasing. Surveillance for typhoid fever is hampered by the lack of laboratory resources for rapid diagnosis, culture confirmation and antimicrobial susceptibility testing. Nonetheless, in 2010, typhoid fever was estimated to cause 725 incident cases and 7 deaths per 100,000 person years in sub-Saharan Africa. Efforts for prevention and outbreak control are challenged by limited access to safe drinking water and sanitation and by a lack of resources to initiate typhoid immunization. A comprehensive approach to typhoid fever prevention including laboratory and epidemiologic capacity building, investments in water, sanitation and hygiene and reconsideration of the role of currently available vaccines could significantly reduce the disease burden. Targeted vaccination using currently available typhoid vaccines should be considered as a short- to intermediate-term risk reduction strategy for high-risk groups across sub-Saharan Africa.

  16. Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

    Science.gov (United States)

    Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, Tunc

    2014-05-01

    New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (Pasthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. PMID:24613203

  17. Effects of “Danzhi Decoction” on Chronic Pelvic Pain, Hemodynamics, and Proinflammatory Factors in the Murine Model of Sequelae of Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Xiaoling Bu

    2015-01-01

    Full Text Available Objective. To evaluate the effect of Danzhi decoction (DZD on chronic pelvic pain (CPP, hemodynamics, and proinflammatory factors of sequelae of pelvic inflammatory diseases (SPID in murine model. Methods. SPID mice were randomly treated with high-dose DZD, mid-dose DZD, low-dose DZD, aspirin, and vehicle for 3 estrous circles. The Mouse Grimace Scale (MGS was performed to evaluate CPP; blood flows of the upper genital tract, pelvic wall, and mesentery were used to assess hemodynamics in SPID mice; expressions of vascular endothelial growth factor (VEGF, angiopoietin-2 (Ang-2, and osteopontin (OPN were measured by Western blot and immunochemistry. Results. Treatment with dose-dependent DZD significantly decreased the MGS scores, accelerated blood flows of the pelvis, and reduced expressions of VEGF, Ang-2, and OPN in the upper genital tract. Conclusions and Discussions. DZD was effective in relieving CPP and improving hemodynamics of the pelvic blood-stasis microenvironment in SPID mice. There was a relationship between CPP and the pelvic blood-stasis microenvironment. Furthermore, DZD might play a positive role in the anti-inflammatory process.

  18. LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease.

    Directory of Open Access Journals (Sweden)

    Karryn T Grafton

    Full Text Available BACKGROUND: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its anti-angiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the αVβ3 integrin. METHODS: Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR was then examined using a murine model of chronic OVA-induced allergic airways disease. RESULTS: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. CONCLUSION: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.

  19. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa

    Science.gov (United States)

    Wong, Vanessa K.; Holt, Kathryn E.; Okoro, Chinyere; Baker, Stephen; Pickard, Derek J.; Marks, Florian; Page, Andrew J.; Olanipekun, Grace; Munir, Huda; Alter, Roxanne; Fey, Paul D.; Feasey, Nicholas A.; Weill, Francois-Xavier; Le Hello, Simon; Hart, Peter J.; Kariuki, Samuel; Breiman, Robert F.; Gordon, Melita A.; Heyderman, Robert S.; Jacobs, Jan; Lunguya, Octavie; Msefula, Chisomo; MacLennan, Calman A.; Keddy, Karen H.; Smith, Anthony M.; Onsare, Robert S.; De Pinna, Elizabeth; Nair, Satheesh; Amos, Ben; Dougan, Gordon; Obaro, Stephen

    2016-01-01

    Background The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid. PMID:27657909

  20. Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

    Science.gov (United States)

    Arsenijevic, D; Girardier, L; Seydoux, J; Chang, H R; Dulloo, A G

    1997-05-01

    The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery. PMID:9176193

  1. MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.

    Directory of Open Access Journals (Sweden)

    Nancy Garbacki

    Full Text Available BACKGROUND: miRNAs are now recognized as key regulator elements in gene expression. Although they have been associated with a number of human diseases, their implication in acute and chronic asthma and their association with lung remodelling have never been thoroughly investigated. METHODOLOGY/PRINCIPAL FINDINGS: In order to establish a miRNAs expression profile in lung tissue, mice were sensitized and challenged with ovalbumin mimicking acute, intermediate and chronic human asthma. Levels of lung miRNAs were profiled by microarray and in silico analyses were performed to identify potential mRNA targets and to point out signalling pathways and biological processes regulated by miRNA-dependent mechanisms. Fifty-eight, 66 and 75 miRNAs were found to be significantly modulated at short-, intermediate- and long-term challenge, respectively. Inverse correlation with the expression of potential mRNA targets identified mmu-miR-146b, -223, -29b, -29c, -483, -574-5p, -672 and -690 as the best candidates for an active implication in asthma pathogenesis. A functional validation assay was performed by cotransfecting in human lung fibroblasts (WI26 synthetic miRNAs and engineered expression constructs containing the coding sequence of luciferase upstream of the 3'UTR of various potential mRNA targets. The bioinformatics analysis identified miRNA-linked regulation of several signalling pathways, as matrix metalloproteinases, inflammatory response and TGF-β signalling, and biological processes, including apoptosis and inflammation. CONCLUSIONS/SIGNIFICANCE: This study highlights that specific miRNAs are likely to be involved in asthma disease and could represent a valuable resource both for biological makers identification and for unveiling mechanisms underlying the pathogenesis of asthma.

  2. The role of cell-mediated immunity in typhoid.

    Science.gov (United States)

    Mabel, T J; Paniker, C K

    1979-06-01

    The cell-mediated immunity in typhoid was assessed by the leukocyte migration inhibition test and delayed hypersensitivity skin test in 60 clinical typhoid patients. The property of leukocyte migration inhibition appeared first and was positive in 28 of 60 (46.7%) patients on admission and 45 of 60 (75%) at the time of discharge. This difference was definitely more in blood culture positive patients. The delayed hypersensitivity appeared later and was positive in 18 of 60 (30%) on admission and 31 of 60 (51.7%) at the time of discharge. Patients with positive cellular-immune response against typhoid antigen did not develop relapse. On the whole cell-mediated immunity seems to play an important role in typoid. The control groups--the medical and surgical patients, doctors, clinical students and preclinical students--showed positive cellular immune response of 43.3 81.3, 40.7 and 25% respectively. The significance of these results is discussed.

  3. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.

    Science.gov (United States)

    Oghumu, Steve; Knobloch, Thomas J; Terrazas, Cesar; Varikuti, Sanjay; Ahn-Jarvis, Jennifer; Bollinger, Claire E; Iwenofu, Hans; Weghorst, Christopher M; Satoskar, Abhay R

    2016-09-15

    Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. PMID:27164411

  4. Outcome of surgical treatment of intestinal perforation in typhoid fever

    Institute of Scientific and Technical Information of China (English)

    Aziz; Sümer; zgür; Kemik; Ahmet; Cumhur; Dülger; Aydemir; Olmez; Ismail; Hasirci; Erol; Kisli; Vedat; Bayrak; Gulay; Bulut; etin; Kotan

    2010-01-01

    AIM:To represent our clinical experience in the treatment of intestinal perforation arising from typhoid fever.METHODS:The records of 22 surgically-treated patients with typhoid intestinal perforation were evaluated retrospectively.RESULTS:There were 18 males and 4 females,mean age 37 years(range,8-64 years).Presenting symptoms were fever,abdominal pain,diarrhea or constipation.Sixteen cases were subjected to segmental resection and end-to-end anastomosis,while 3 cases received 2-layered primary repair foll...

  5. Beneficial Effect of Brewers' Yeast Extract on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Takashi Takahashi

    2006-01-01

    Full Text Available The aim of this study was to assess the effect of Brewers' yeast extract (BYE on daily activity in a mouse model of chronic fatigue syndrome (CFS. CFS was induced by repeated injection of Brucella abortus (BA antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW and survival in both groups was monitored during the observation period. Spleen weight (SW, SW/BW ratio, percent splenic follicular area and expression levels of interferon-γ (IFN-γ and interleukin-10 (IL-10 mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-γ and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.

  6. Beneficial effect of brewers' yeast extract on daily activity in a murine model of chronic fatigue syndrome.

    Science.gov (United States)

    Takahashi, Takashi; Yu, Fei; Zhu, Shi-Jie; Moriya, Junji; Sumino, Hiroyuki; Morimoto, Shigeto; Yamaguchi, Nobuo; Kanda, Tsugiyasu

    2006-03-01

    The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.

  7. Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh

    OpenAIRE

    K M Shahunja; Leung, Daniel T.; Ahmed, Tahmeed; Bardhan, Pradip Kumar; Ahmed, Dilruba; Qadri, Firdausi; Ryan, Edward T.; Chisti, Mohammod Jobayer

    2015-01-01

    Background: Non-typhoidal Salmonella (NTS) and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia. Methodology We performed a retrospective age-matched case-control study of patients admitted t...

  8. Duration of Vi antibodies in participants vaccinated with Typhim Vi (Typhoid Vi polysaccharide vaccine) in an area not endemic for typhoid fever.

    Science.gov (United States)

    Froeschle, James E; Decker, Michael D

    2010-02-10

    After a single injection of Typhim Vi (typhoid Vi polysaccharide vaccine), serum antibody concentrations were monitored for 3 years in 37 adults who resided where typhoid fever was not endemic. Anti-Vi antibody concentrations declined progressively during the study, to levels that support the current US recommendation for revaccination every 2 years.

  9. Specific and cross-reactive antibody response to typhoid vaccination in humans

    OpenAIRE

    Pakkanen, Sari

    2014-01-01

    Diseases caused by Salmonella (S.) comprise a serious health problem worldwide. Salmonella can cause enteric fever (typhoid fever and paratyphoid fever, caused by S. Typhi and S. Paratyphi A/B/C, respectively) or diarrhea (caused by non-typhoidal Salmonella, NTS serotypes). NTS serotypes can also cause severe invasive salmonellosis (iNTS). Typhoid fever is the only one of these diseases against which there are vaccines in clinical use: the oral live attenuated whole-cell vaccine Salmonella Ty...

  10. Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010

    Directory of Open Access Journals (Sweden)

    Geoffrey C. Buckle

    2012-06-01

    Full Text Available Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies.

  11. Typhoid Fever Presenting With Acute Renal Failure And Hepatitis Simultaneously - A Rare Presentation

    Directory of Open Access Journals (Sweden)

    Rajput R.

    2016-05-01

    Full Text Available Typhoid fever is an important health problem worldwide but its incidence is more in developing countries. Hepatic involvement is common, but both hepatic and renal involvement is rare in typhoid fever. We report a case of typhoid fever presenting with hepatitis and acute renal failure. A 17 year old male presenting with fever and pain abdomen was found to have raised blood urea, creatinine, liver enzymes and bilirubin. Widal and typhidot (IgM,IgG test were positive. His symptoms subsided and deranged parameters resolved with treatment of typhoid fever.

  12. [Typhoid fever imported from the tropic in Poland].

    Science.gov (United States)

    Olszyńiska-Krowicka, Maria; Borkowski, Piotr Karol

    2007-01-01

    We present three cases of typhoid fever imported to Poland from India in the beginning of the year 2006 treated in our Zoonosis and Tropical Medicine Department. Two of them, with mild course of the disease, were vaccinated with Typhim Vi vaccine, the third didn't obtain any, and had very heavy, almost classical course of the disease. All of them behaved in India in improper way, probably also because were convinced they were protected by the vaccine. We emphasize that proper prophylaxis against typhoid fever for travelers should consist of vaccination with two vaccines, oral Ty 21a and parenteral Typhim Vi and it doesn't release travelers from avoiding risky behavior.

  13. Genomics of immune response to typhoid and cholera vaccines.

    Science.gov (United States)

    Majumder, Partha P

    2015-06-19

    Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways.

  14. Safety and immunogenicity of combined rabies and typhoid fever immunization.

    Science.gov (United States)

    Fritzell, C; Rollin, P E; Touir, M; Sureau, P; Teulieres, L

    1992-01-01

    The prevalence of rabies and typhoid fever in many developing countries poses a serious health hazard to travellers. The development of a combined immunization schedule would be advantageous. A study was performed on 104 adult volunteers using purified Vero cell rabies vaccine and Typhim Vi, a purified capsular polysaccharide, either separately or in combination. No significant difference was observed in immunogenicity or tolerance between the two groups. A 3-year follow-up study is planned.

  15. The sad and tragic life of Typhoid Mary.

    Science.gov (United States)

    Brooks, J

    1996-03-15

    As society grapples with contemporary moral questions raised by the barring of HIV-infected people from jobs and even crossing some national borders, it is probably useful to re-examine the case of Typhoid Mary. The case of Mary Mallon shows how an earlier age resolved the conflict that arises when society's right to protect itself from unnecessary exposure to disease impinges on the liberty of individual citizens. PMID:8634973

  16. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever.

    Science.gov (United States)

    Klugman, K P; Gilbertson, I T; Koornhof, H J; Robbins, J B; Schneerson, R; Schulz, D; Cadoz, M; Armand, J

    1987-11-21

    The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination.

  17. Salmonella enterica Serovar Virchow Bacteremia Presenting as Typhoid-Like Illness in an Immunocompetent Patient ▿

    OpenAIRE

    Eckerle, Isabella; Zimmermann, Stefan; Kapaun, Annette; Junghanss, Thomas

    2010-01-01

    We report a typhoid-like illness with fever and altered consciousness in a 22-year-old man with growth of Salmonella enterica serovar Virchow in blood and stool culture. Bacteremia and invasive disease due to non-typhoid salmonellae (NTS) are known in severely immunocompromised patients, but so far have not been described in immunocompetent adults.

  18. Effectiveness of Vi capsular polysaccharide typhoid vaccine among children: a cluster randomized trial in Karachi, Pakistan

    NARCIS (Netherlands)

    Khan, M.I.; Soofi, S.B.; Ochiai, R.L.; Habib, M.A.; Sahito, S.M.; Nizami, S.Q.; Acosta, C.J.; Clemens, J.D.; Bhutta, Z.A.; Group, D.T.K.V.E.S.

    2012-01-01

    BACKGROUND: Typhoid fever is endemic in Karachi, with an incidence among children ranging from 170 to 450 per 100,000 child-years. Vaccination strategies are important for prevention, and the Vi capsular polysaccharide (ViCPS) vaccine has been shown to be effective in reducing the burden of typhoid

  19. An outbreak of typhoid fever, Xing-An County, People's Republic of China, 1999: estimation of the field effectiveness of Vi polysaccharide typhoid vaccine.

    Science.gov (United States)

    Yang, H H; Kilgore, P E; Yang, L H; Park, J K; Pan, Y F; Kim, Y; Lee, Y J; Xu, Z Y; Clemens, J D

    2001-06-15

    To evaluate the effectiveness of Vi polysaccharide vaccine (Vi vaccine) in preventing typhoid fever, an analysis was done of an outbreak of typhoid fever among students attending a middle school in the People's Republic of China, where Vi vaccine is licensed for use. Vi vaccine effectiveness was analyzed by using Cox proportional hazards modeling to account for the time-dependent nature of vaccination and illness status during the outbreak. Among 1260 students who had been immunized before the outbreak, receipt of Vi vaccine was associated with 73% (95% confidence interval [CI], 32%-89%) protection. Among the additional 441 students immunized during the outbreak, receipt of Vi vaccine was associated with 71% (95% CI, -9% to 92%) protection. These results provide the first evidence about the effectiveness of Vi vaccine when deployed routinely in a typhoid-endemic area and support the use of Vi vaccine as a public health tool to control typhoid fever.

  20. Analysis of the murine renal transcriptoma in conditions of acute and chronic exposure to uranium; Analyse du transcriptome renal murin dans des conditions d'exposition aigue et chronique a l'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Taulan, M

    2004-06-01

    The principal objective of this work was to evaluate the molecular alterations induced by uranium. For this, were used classical approaches of toxicology and implementation of a global analysis technique: S.A.G.E. (serial analysis of gene expression). After acute contamination, was brought to the shore an alteration of the renal function and a catalogue of different transcripts representative of molecular events consecutive to uranium incorporation was defined. More than 14 000 transcripts have been identified, among which 224 genes that present a variation in gene expression. These last ones have been classified in different categories of cell processes as inflammation, oxidative stress, cell transporters, signal transduction, apoptosis, metabolism and catabolism. The same study was made for a chronic exposure. This study shows that the chronic uranium ingestion changes numerous cell processes as these ones previously noticed. The whole of these data has allowed to validate the use of the genomic approach S.A.G.E. in the field of toxicology, by establishing a profile of gene expression of events relative to an uranium intoxication. The analysis of molecular consequences should allow to find early markers of an uranium contamination, means more efficient of this actinide elimination and new therapies targets. (N.C.)

  1. Vaccination against typhoid fever in travellers: a cost-effectiveness approach.

    Science.gov (United States)

    Papadimitropoulos, V; Vergidis, P I; Bliziotis, I; Falagas, M E

    2004-08-01

    Analysis of data on the incidence of typhoid fever and the costs of vaccination of travellers to the developing world indicates that vaccination may not be cost-effective for travel to countries with a moderate-to-high endemicity. It may be reasonable to selectively vaccinate travellers to countries with a very high incidence of typhoid fever, and particularly those who are visiting relatives or who will be in close contact with the local population. Vaccination of travellers on standard tourist itineraries is probably not necessary. The basic preventative measure for typhoid fever should be the avoidance of potentially contaminated food and drink.

  2. Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

    Directory of Open Access Journals (Sweden)

    Miriam Maraslioglu

    2014-01-01

    Full Text Available Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κBEGFP reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS. We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.

  3. Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the IκB Kinase Inhibitor NEMO Binding Domain Peptide1

    OpenAIRE

    Davé, Shaival H.; Tilstra, Jeremy S.; Matsuoka, Katsuyoshi; Li, Fengling; Karrasch, Thomas; Uno, Jennifer K.; Sepulveda, Antonia R; Jobin, Christian; Baldwin, Albert S.; Paul D Robbins; Plevy, Scott E.

    2007-01-01

    The NF-κB family of transcription factors is a central regulator of chronic inflammation. The phosphorylation of IκB proteins by the IκB kinase (IKK) complex (IKKα, IKKβ, and NF-κB essential modulator or NEMO) is a key step in NF-κB activation. Peptides corresponding to the NEMO binding domain (NBD) of IKK blocks NF-κB activation without inhibiting basal NF-κB activity. In this report, we determined the effects of the IKK inhibitor peptide (NBD) in a model of spontaneously occurring chronic m...

  4. SALMONELLA HEPATITIS (ANALYSIS OF HEPATIC INVOLVEMENT IN 107 PATIENTS WITH TYPHOID FEVER

    Directory of Open Access Journals (Sweden)

    M. Rasoolinejad

    2003-07-01

    Full Text Available Recognition of typhoid hepatitis is important since it has to be differentiated from other common ailments in our country such as viral, malarial or amoebic hepatitis. Early institution of specific therapy in cases of typhoid hepatitis carries a good prognosis. In our study, 107 patients with positive blood or bone marrow cultures for Salmonella typhi, were evaluated for hepatomegaly and abnormal serum liver enzymes, PT and alkaline phosphatase. The clinical features of typhoid fever with hepatic involvement include: fever 100%, hepatomegaly 52.3%, clinical jaundice 1.8%, rising in ALT 71.1%, AST 24.2%, Alkaline phosphatase 23.3% and abnormal PT 63.5%. Both clinical and biochemical abnormalities were seen in 22.4% of our patients. In patients with fever and jaundice with or without abnormality in liver enzymes, we must keep typhoid hepatitis in mind.

  5. Severity of infection and seasonal variation of non-typhoid Salmonelle occurence in humans

    DEFF Research Database (Denmark)

    Gradel, K.O.; Dethlefsen, Claus; Schønheyder, H.C.;

    2007-01-01

    Non-typhoid Salmonella infections may present as severe gastroenteritis necessitatinghospitalization and some patients become septic with bacteraemia. We hypothesized that theseasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increasedseverity of infection. We...... examined the seasonal variation of non-typhoid Salmonella infections inthree patient groups with differing severity of infection: outpatients treated for gastroenteritis(n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia(n=113). The study was population......-based and included all non-typhoid Salmonella patients ina Danish county from 1994 to 2003. A periodic regression model was used to compute thepeak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4·3 [95%confidence interval (CI) 3·6–5.0] for outpatients with gastroenteritis, 3...

  6. What Have We Learned From the Typhoid Fever Surveillance in Africa Program?

    Science.gov (United States)

    Baker, Stephen; Hombach, Joachim; Marks, Florian

    2016-03-15

    The Typhoid Fever Surveillance in Africa Program (TSAP) was established in 2009 to fill the data void concerning invasive Salmonella disease in sub-Saharan Africa, and to specifically estimate the burden of bloodstream infections caused by the key pathogen, Salmonella enterica serovar Typhi. TSAP has achieved this ambitious target, finding high incidences of typhoid fever in both rural and urban populations in several countries in sub-Saharan Africa. The results of TSAP will undoubtedly dictate the direction of future typhoid fever research in Africa, and at last provides a key piece of the disease burden jigsaw puzzle. With the dawn of new Vi conjugate vaccines against Salmonella Typhi, the next priority for the typhoid community must be providing the required data on these vaccines so they can be licensed and provided to those in high-risk groups and locations across sub-Saharan Africa.

  7. Multifocal choroiditis following simultaneous hepatitis A, typhoid, and yellow fever vaccination

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    Escott S

    2013-02-01

    Full Text Available Sarah Escott, Ahmad B Tarabishy, Frederick H DavidorfHavener Eye Institute, The Ohio State University, Columbus, OH, USAAbstract: The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.Keywords: multifocal choroiditis, vaccination, hepatitis A, typhoid, yellow fever

  8. Superior Sagittal Sinus Thrombosis Complicating Typhoid Fever in a Teenager

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    P. O. Okunola

    2012-01-01

    Full Text Available Cerebral venous sinus (sinovenous thrombosis (CSVT is a rare life-threatening disorder in childhood that is often misdiagnosed. CSVT encompasses cavernous sinus thrombosis, lateral sinus thrombosis, and superior sagittal sinus thrombosis (SSST. We present an adolescent girl who was well until two weeks earlier when she had a throbbing frontal headache and fever with chills; she later had dyspnoea, jaundice, melena stool, multiple seizures, nuchal rigidity, and monoparesis of the right lower limb a day before admission. Urine test for Salmonella typhi Vi antigen was positive, and Widal reaction was significant. Serial cranial computerized tomography scans revealed an expanding hypodense lesion in the parafalcine region consistent with SSST or a parasagittal abscess. Inadvertent left parietal limited craniectomy confirmed SSST. She recovered completely with subsequent conservative management. Beyond neuropsychiatric complications of Typhoid fever, CSVT should be highly considered when focal neurologic deficits are present.

  9. Risk factors associated with typhoid fever in children aged 2-16 years in Karachi, Pakistan.

    Science.gov (United States)

    Khan, M I; Ochiai, R L; Soofi, S B; Von-Seidlein, L; Khan, M J; Sahito, S M; Habib, M A; Puri, M K; Park, J K; You, Y A; Ali, M; Nizami, S Q; Acosta, C J; Bradley-Sack, R; Clemens, J D; Bhutta, Z A

    2012-04-01

    We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household- and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0·89, 95% confidence interval (CI) 0·83-0·95], was higher with an increase in population density (RR 1·13, 95% CI 1·05-1·21) and was lower in the households using a safe drinking-water source (RR 0·63, 95% CI 0·41-0·99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.

  10. Low sensitivity of counter-current immuno-electrophoresis for serodiagnosis of typhoid fever.

    Science.gov (United States)

    Sharma, M; Datta, U; Roy, P; Verma, S; Sehgal, S

    1997-12-01

    Counter-current immuno-electrophoresis was evaluated as a diagnostic test for the serodiagnosis of typhoid fever with somatic (O), flagellar (H) and capsular polysaccharide (Vi) antigens of Salmonella typhi on the sera of patients who were blood culture positive (confirmed typhoid cases) or had high Widal agglutination titres, > or = 320, (presumptive typhoid cases). Of the 37 sera from confirmed cases, 30% showed positivity with O antigen, 24% with H antigens and 51% with Vi antigen. In patients with a presumptive diagnosis, 45% were positive for O antibody, 27% for flagellar antibody and 52% for Vi antibody. When all three antigens were combined the reactivity to any of the antigens was found to be 59% in confirmed typhoid cases, 79% in presumptive typhoid cases and 93% in patients who were simultaneously positive by blood culture and Widal agglutination. However, none of the sera from 45 controls gave a positive precipitation reaction with any of the antigens. It is concluded that counter-current immuno-electrophoresis is a rapid test with low sensitivity and high specificity with Vi antigen, a panel of antigens being most effective, and is, therefore, recommended for rapid diagnosis of typhoid fever.

  11. Neutralization of TSLP Inhibits Airway Remodeling in a Murine Model of Allergic Asthma Induced by Chronic Exposure to House Dust Mite

    OpenAIRE

    Chen, Zhuang-Gui; Zhang, Tian-Tuo; Li, Hong-Tao; Chen, Fen-Hua; Zou, Xiao-Ling; Ji, Jing-Zhi; Chen, Hong

    2013-01-01

    Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs) through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of ai...

  12. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  13. Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid.

    Science.gov (United States)

    Kinnear, Clare L; Strugnell, Richard A

    2015-01-01

    Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.

  14. Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid.

    Directory of Open Access Journals (Sweden)

    Clare L Kinnear

    Full Text Available Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.

  15. A review of typhoid fever transmission dynamic models and economic evaluations of vaccination.

    Science.gov (United States)

    Watson, Conall H; Edmunds, W John

    2015-06-19

    Despite a recommendation by the World Health Organization (WHO) that typhoid vaccines be considered for the control of endemic disease and outbreaks, programmatic use remains limited. Transmission models and economic evaluation may be informative in decision making about vaccine programme introductions and their role alongside other control measures. A literature search found few typhoid transmission models or economic evaluations relative to analyses of other infectious diseases of similar or lower health burden. Modelling suggests vaccines alone are unlikely to eliminate endemic disease in the short to medium term without measures to reduce transmission from asymptomatic carriage. The single identified data-fitted transmission model of typhoid vaccination suggests vaccines can reduce disease burden substantially when introduced programmatically but that indirect protection depends on the relative contribution of carriage to transmission in a given setting. This is an important source of epidemiological uncertainty, alongside the extent and nature of natural immunity. Economic evaluations suggest that typhoid vaccination can be cost-saving to health services if incidence is extremely high and cost-effective in other high-incidence situations, when compared to WHO norms. Targeting vaccination to the highest incidence age-groups is likely to improve cost-effectiveness substantially. Economic perspective and vaccine costs substantially affect estimates, with disease incidence, case-fatality rates, and vaccine efficacy over time also important determinants of cost-effectiveness and sources of uncertainty. Static economic models may under-estimate benefits of typhoid vaccination by omitting indirect protection. Typhoid fever transmission models currently require per-setting epidemiological parameterisation to inform their use in economic evaluation, which may limit their generalisability. We found no economic evaluation based on transmission dynamic modelling, and no

  16. Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: an epidemiologic investigation.

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    James Sejvar

    Full Text Available BACKGROUND: The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness. OBJECTIVE: Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique METHODS: Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture. We gathered demographic and clinical information, examined patients, and evaluated a subset of patients 11 months after onset. A sample of persons with and without neurologic signs was tested for vitamin B6 and B12 levels and urinary thiocyanate. RESULTS: Between March - November 2009, 303 cases of typhoid fever were identified. Forty (13% persons had objective neurologic findings, including 14 confirmed by culture/serology; 27 (68% were hospitalized, and 5 (13% died. Seventeen (43% had a constellation of upper motor neuron findings, including hyperreflexia, spasticity, or sustained ankle clonus. Other neurologic features included ataxia (22, 55%, parkinsonism (8, 20%, and tremors (4, 10%. Brain MRI of 3 (ages 5, 7, and 18 years demonstrated cerebral atrophy but no other abnormalities. Of 13 patients re-evaluated 11 months later, 11 recovered completely, and 2 had persistent hyperreflexia and ataxia. Vitamin B6 levels were markedly low in typhoid fever patients both with and without neurologic signs. CONCLUSIONS: Neurologic signs may complicate typhoid fever, and the diagnosis should be considered in persons with acute febrile neurologic illness in endemic areas.

  17. A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children

    NARCIS (Netherlands)

    T.H. Tran; T.D. Nguyen; T.T. Nguyen; T.T.V. Ninh; N.B.C. Tran; V.M.H. Nguyen; T.T.N. Tran; T.T. Cao; V.M. Pham; T.C.B. Nguyen; T.D.H. Tran; V.T. Pham; S.D. To; J.I. Campbell; E. Stockwell; C. Schultsz; C.P. Simmons; C. Glover; W. Lam; F. Marques; J.P. May; A. Upton; R. Budhram; G. Dougan; J. Farrar; V.V.C. Nguyen; C. Dolecek

    2010-01-01

    Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-) ssaV

  18. The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium

    Directory of Open Access Journals (Sweden)

    Kersting S

    2013-05-01

    Full Text Available Sabine Kersting,1* Volker Behrendt,1* Jonas Kersting,1 Kirstin Reinecke,3 Christoph Hilgert,1 Ingo Stricker,2 Thomas Herdegen,3 Monika S Janot,1 Waldemar Uhl,1 Ansgar M Chromik1 1Department of General and Visceral Surgery, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany; 2Department of Pathology, Ruhr University of Bochum, Bochum, Germany; 3Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany *The two authors Sabine Kersting and Volker Behrendt contributed equally to this work Purpose: The c-Jun N-terminal kinases (JNK are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS model of chronic colitis. Methods: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%. Mice in the intervention groups received subcutaneous administration of 1 µg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4+ and CD8+ cells was also carried out. Results: Administration of 1 µg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS. As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4+ and CD8+ cells was reduced in mice treated with D-JNKI-1 (not

  19. Typhidot (IgM as a reliable and rapid diagnostic test for typhoid fever

    Directory of Open Access Journals (Sweden)

    Sushma Krishna

    2011-01-01

    Full Text Available Introduction: Typhoid fever still continues to be a major public health problem, particularly in developing countries. A simple, reliable, affordable, and rapid diagnostic test has been a long-felt need of the clinicians. We, therefore, prospectively evaluated the sensitivity and specificity of Typhidot (IgM, a serological test to identify IgM antibodies against Salmonella typhi. Materials and Methods: The study was carried out in the Department of Microbiology, Apollo Hospital, Bangalore between January 2009 and March 2009 on a total of 186 samples from clinically suspected febrile patients. Blood culture as well as Typhidot test was performed for each of the cases. Results: Out of 61 clinically diagnosed typhoid fever, 50 were blood culture positive for S. typhi all 50 were Typhidot (IgM positive and 11 were missed out on both. The sensitivity, specificity, positive and negative predictive values of the test using blood culture as gold standard were 100%, 95.5%, 89.2%, and 100%, respectively for typhoid fever. Conclusion: Typhidot (IgM test is rapid, easy to perform, and reliable for diagnosing typhoid fever, and useful for small, less equipped laboratories as well as for the laboratories with better facilities in typhoid endemic countries.

  20. Impact of a targeted typhoid vaccination campaign following cyclone Tomas, Republic of Fiji, 2010.

    Science.gov (United States)

    Scobie, Heather M; Nilles, Eric; Kama, Mike; Kool, Jacob L; Mintz, Eric; Wannemuehler, Kathleen A; Hyde, Terri B; Dawainavesi, Akanisi; Singh, Sheetalpreet; Korovou, Samuel; Jenkins, Kylie; Date, Kashmira

    2014-06-01

    After a category 4 cyclone that caused extensive population displacement and damage to water and sanitation infrastructure in Fiji in March 2010, a typhoid vaccination campaign was conducted as part of the post-disaster response. During June-December 2010, 64,015 doses of typhoid Vi polysaccharide vaccine were administered to persons ≥ 2 years of age, primarily in cyclone-affected areas that were typhoid endemic. Annual typhoid fever incidence decreased during the post-campaign year (2011) relative to preceding years (2008-2009) in three subdivisions where a large proportion of the population was vaccinated (incidence rate ratios and 95% confidence intervals: 0.23, 0.13-0.41; 0.24, 0.14-0.41; 0.58, 0.40-0.86), and increased or remained unchanged in 12 subdivisions where little to no vaccination occurred. Vaccination played a role in reducing typhoid fever incidence in high-incidence areas after a disaster and should be considered in endemic settings, along with comprehensive control measures, as recommended by the World Health Organization.

  1. The contribution of neighbours to an individual's risk of typhoid outcome.

    Science.gov (United States)

    Chao, D L; Park, J K; Marks, F; Ochiai, R L; Longini, I M; Halloran, M E

    2015-12-01

    An individual's risk of infection from an infectious agent can depend on both the individual's own risk and protective factors and those of individuals in the same community. We hypothesize that an individual's exposure to an infectious agent is associated with the risks of infection of those living nearby, whether their risks are modified by pharmaceutical interventions or by other factors, because of the potential for transmission from them. For example, unvaccinated individuals living in a highly vaccinated community can benefit from indirect protection, or living near more children in a typhoid-endemic region (where children are at highest risk) might result in more exposure to typhoid. We tested this hypothesis using data from a cluster-randomized typhoid vaccine trial. We first estimated each individual's relative risk of confirmed typhoid outcome using their vaccination status and age. We defined a new covariate, potential exposure, to be the sum of the relative risks of all who live within 100 m of each person. We found that potential exposure was significantly associated with an individual's typhoid outcome, and adjusting for potential exposure affected estimates of vaccine efficacy. We suggest that it is useful and feasible to adjust for spatially heterogeneous distributions of individual-level risk factors, but further work is required to develop and test such approaches.

  2. Impact of Vi vaccination on spatial patterns of typhoid fever in the slums of Kolkata, India.

    Science.gov (United States)

    Ali, Mohammad; Sur, Dipika; Kim, Deok Ryun; Kanungo, Suman; Bhattacharya, Sujit K; Manna, Byomkesh; Ochiai, R Leon; Clemens, John

    2011-11-01

    A mass typhoid Vi vaccination campaign was carried out among approximately 60,000 slum residents of Kolkata, India. This study evaluated the impact of the campaign on spatial patterns of typhoid fever. Eighty contiguous residential groups of households in the study area were randomized to receive either a single dose of the Vi polysaccharide vaccine or a single dose of the inactivated hepatitis A vaccine as the control agent. Persons aged two years and older were eligible to receive the vaccine. Vaccine protection against typhoid fever was monitored for two years after vaccination at both outpatient and inpatient facilities serving the study population. Geographic analytic and mapping tools were used in the analysis. Spatial randomness of the disease was observed during the pre-vaccination period, which turned into a significant pattern after vaccination. The high-risk areas for typhoid were observed in the area dominated by the control clusters, and the low-risk areas were in the area dominated by the Vi clusters. Furthermore, the control clusters surrounded by the Vi clusters were low risk for typhoid fever. The results demonstrated the ability of mass vaccination to change the spatial patterns of disease through the creation of spatial barriers to transmission of the disease. Understanding and mapping the disease risk could be useful for designing a community-based vaccination strategy to control disease.

  3. The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.

    Science.gov (United States)

    Pham Thanh, Duy; Thompson, Corinne N; Rabaa, Maia A; Sona, Soeng; Sopheary, Sun; Kumar, Varun; Moore, Catrin; Tran Vu Thieu, Nga; Wijedoru, Lalith; Holt, Kathryn E; Wong, Vanessa; Pickard, Derek; Thwaites, Guy E; Day, Nicholas; Dougan, Gordon; Turner, Paul; Parry, Christopher M; Baker, Stephen

    2016-06-01

    Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1-11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines.

  4. The role of epidemiology in the introduction of vi polysaccharide typhoid fever vaccines in Asia.

    Science.gov (United States)

    Acosta, Camilo J; Galindo, Claudia M; Ochiai, R Leon; Danovaro-Holliday, M Carolina; Page, Anne-Laure; Thiem, Vu Dinh; Park, Jin Kyoung; Park, Eunsik; Koo, Hyewon; Wang, Xuan-Yi; Abu-Elyazeed, Remon; Ali, Mohammad; Albert, M John; Ivanoff, Bernard; Pang, Tikki; Xu, Zhi-Yi; Clemens, John D

    2004-09-01

    Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction.

  5. Synergistic Activity of Deguelin and Fludarabine in Cells from Chronic Lymphocytic Leukemia Patients and in the New Zealand Black Murine Model

    Science.gov (United States)

    Rebolleda, Nerea; Losada-Fernandez, Ignacio; Perez-Chacon, Gema; Castejon, Raquel; Rosado, Silvia; Morado, Marta; Vallejo-Cremades, Maria Teresa; Martinez, Andrea; Vargas-Nuñez, Juan A.

    2016-01-01

    B-cell chronic lymphocytic leukemia (CLL) remains an incurable disease, and despite the improvement achieved by therapeutic regimes developed over the last years still a subset of patients face a rather poor prognosis and will eventually relapse and become refractory to therapy. The natural rotenoid deguelin has been shown to induce apoptosis in several cancer cells and cell lines, including primary human CLL cells, and to act as a chemopreventive agent in animal models of induced carcinogenesis. In this work, we show that deguelin induces apoptosis in vitro in primary human CLL cells and in CLL-like cells from the New Zealand Black (NZB) mouse strain. In both of them, deguelin dowregulates AKT, NFκB and several downstream antiapoptotic proteins (XIAP, cIAP, BCL2, BCL-XL and survivin), activating the mitochondrial pathway of apoptosis. Moreover, deguelin inhibits stromal cell-mediated c-Myc upregulation and resistance to fludarabine, increasing fludarabine induced DNA damage. We further show that deguelin has activity in vivo against NZB CLL-like cells in an experimental model of CLL in young NZB mice transplanted with spleen cells from aged NZB mice with lymphoproliferation. Moreover, the combination of deguelin and fludarabine in this model prolonged the survival of transplanted mice at doses of both compounds that were ineffective when administered individually. These results suggest deguelin could have potential for the treatment of human CLL. PMID:27101369

  6. Jir hur a Fermented Millet (Penisitum typhoidism Product of Sudan

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    K.H. Samah

    2011-07-01

    Full Text Available Jir hur is a traditional fermented food of the Fur tribe of western Sudan prepared from bulrush millet (Penisitum typhoidism. The microbiological changes during the fermentation stages were monitored. LAB count increased from 4.48 in raw millet to 7.19 log/cfug in jir hur and yeast count increased from 3.77 to 7.55 log/cfug, respectively with significant changes in pH from 6.66 in raw millet to 3.68 in jir hur. The fermentation of millet into jir was a homo-lactic acid fermentation that involved a complex microbial succession between LAB and yeast. LAB was the predominant microorganisms during the first fermentation with significant increase in yeast counts. Pediococcus halophilus, Pediococcus inopinatus and Pediococcus urinaeequi were the dominant lactic acid bacteria species at all times with the association of Lactobacillus acidophilus and Lactobacillus jensenii at the second fermentation. The yeast species Schizosaccharomyces pombe, Saccharomycods sinensis and Trichosporon adeninovorans were followed in succession during jir fermentation stages.

  7. "Typhoid Mary" and "HIV Jane": responsibility, agency and disease prevention.

    Science.gov (United States)

    Chan, Kit Yee; Reidpath, Daniel D

    2003-11-01

    The construction of disease risks as knowable, calculable and preventable in dominant social science and public health discourses has fostered a certain kind of logic about individual risk and the responsibility for infection. Disease control measures that have developed out of this logic typically fail to recognise the socio-structural roots of many high-risk behaviours that are linked to the spread of infection. Instead, they hold the disease carrier responsible for managing his/her own risk of infection of others, and rely on constraining the agency of the carrier (e.g. by constraining movement, contact or occupation). In occupations associated with a high risk of infection, the idea of responsibility of the actor implicitly raises issues of "professional responsibility". Using the case of "Typhoid Mary" and a hypothetical case of "HIV Jane", this paper explores some of the problems with making sex workers responsible for the prevention of HIV transmission. It argues that for the notion of "responsibility" to make any sense, the HIV-positive person must be in a position to exercise responsibility, and for this they must have agency. PMID:14708397

  8. Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

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    Franklin R Toapanta

    2015-06-01

    Full Text Available A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD- 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h and/or microbiological (S. Typhi bacteremia endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-. Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD- were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h. Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.

  9. The case for a typhoid vaccine probe study and overview of design elements.

    Science.gov (United States)

    Gessner, Bradford D; Halloran, M Elizabeth; Khan, Imran

    2015-06-19

    Recent advances in typhoid vaccine, and consideration of support from Gavi, the Vaccine Alliance, raise the possibility that some endemic countries will introduce typhoid vaccine into public immunization programs. This decision, however, is limited by lack of definitive information on disease burden. We propose use of a vaccine probe study approach. This approach would more clearly assess the total burden of typhoid across different syndromic groups and account for lack of access to care, poor diagnostics, incomplete laboratory testing, lack of mortality and intestinal perforation surveillance, and increasing antibiotic resistance. We propose a cluster randomized trial design using a mass immunization campaign among all age groups, with monitoring over a 4-year period of a variety of outcomes. The primary outcome would be the vaccine preventable disease incidence of prolonged fever hospitalization. Sample size calculations suggest that such a study would be feasible over a reasonable set of assumptions.

  10. Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis

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    Grissom Sherry F

    2009-11-01

    Full Text Available Abstract Background Therapeutic strategies exist for human pulmonary neoplasia, however due to the heterogeneity of the disease, most are not very effective. The innate immunity gene, toll-like receptor 4 (TLR4, protects against chronic pulmonary inflammation and tumorigenesis in mice, but the mechanism is unclear. This study was designed to identify TLR4-mediated gene expression pathways that may be used as prognostic indicators of susceptibility to lung tumorigenesis in mice and provide insight into the mechanism. Methods Whole lung mRNA was isolated from C.C3H-Tlr4Lps-d (BALBLps-d; Tlr4 mutant and BALB/c (Tlr4 normal mice following butylated hydroxytoluene (BHT-treatment (four weekly ip. injections; 150-200 mg/kg/each; "promotion". mRNA from micro-dissected tumors (adenomas and adjacent uninvolved tissue from both strains were also compared 27 wks after a single carcinogen injection (3-methylcholanthrene (MCA, 10 μg/g; "control" or followed by BHT (6 weekly ip. injections; 125-200 mg/kg/each; "progression". Bronchoalveolar lavage fluid was analyzed for inflammatory cell content and total protein determination, a marker of lung hyperpermeability; inflammation was also assessed using immunohistochemical staining for macrophages (F4/80 and lymphocytes (CD3 in mice bearing tumors (progression. Results During promotion, the majority of genes identified in the BALBLps-d compared to BALB/c mice (P Ereg, secreted phosphoprotein 1(Spp1, which can lead to cell growth and eventual tumor development. Inflammation was significantly higher in BALBLps-d compared to BALB/c mice during progression, similar to the observed response during tumor promotion in these strains. Increases in genes involved in signaling through the EGFR pathway (e.g. Ereg, Spp1 were also observed during progression in addition to continued inflammation, chemotactic, and immune response gene expression in the BALBLps-d versus BALB/c mice (P Conclusion This transcriptomic study

  11. Investigation of the response to the enterobacterial common antigen after typhoid vaccination

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    Arlete M. Milhomem

    1987-03-01

    Full Text Available Antibodies against the Salmonella typhi enterobacterial common antigen (ECA and the O and H antigens were investigated in sera from healthy male subjects who had been previously vaccinated with the typhoid vaccine. No serological response to ECA was observed. Sera from subjects not previously vaccinated presented titers of ECA hemagglutinins which quantitatively were related to the presence ofH titers, but not to O agglutinins but with no statistical significance. The results are discussed in relation to the possible protective immunological mechanisms in typhoid fever.

  12. Population-based incidence of typhoid fever in an urban informal settlement and a rural area in Kenya: implications for typhoid vaccine use in Africa.

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    Robert F Breiman

    Full Text Available BACKGROUND: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. METHODS: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. RESULTS: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi bacteremia was 247 cases per 100,000 person-years of observation (pyo with highest rates in children 5-9 years old (596 per 100,000 pyo and 2-4 years old (521 per 100,000 pyo. Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2-4 and 5-9 years old (28 and 18 cases per 100,000 pyo, respectively. Adjusted incidence rates were highest in 2-4 year old urban children (2,243 per 100,000 pyo which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant. CONCLUSIONS: This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.

  13. Clinical and epidemiological features of typhoid fever in Pemba, Zanzibar: assessment of the performance of the WHO case definitions.

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    Kamala Thriemer

    Full Text Available BACKGROUND: The gold standard for diagnosis of typhoid fever is blood culture (BC. Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever. METHODOLOGY/PRINCIPAL FINDINGS: Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1:80. CONCLUSIONS/SIGNIFICANCE: Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.

  14. Orbital cellulitis in course of typhoid fever; Zapalenie tkanki oczodolowej w przebiegu duru brzusznego

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    Nowacka, K.; Szreter, M.; Mikolajewicz, J. [Centrum Zdrwowia Dziecka, Warsaw (Poland)

    1993-12-31

    In 18 months girl with exophthalmus of the left eye and extensive swelling of the soft tissues in both orbits during continued fever was observed. Typhoid fever with a non-typical course and ophthalmic complications were diagnosed on the basis of serological tests. Complete cure after treatment with augmenting was obtained. (author) 10 refs, 2 figs

  15. Detection of non-typhoid Salmonella infection by citrus and citrus extracts in Lao PDR

    Institute of Scientific and Technical Information of China (English)

    Yutaka Midorikawa; Satoshi Nakamura; Rattanaphone Phetsouvanh; Manivanh Vongsouvaht; Kaoru Midorikawa

    2010-01-01

    Objective: To know the current state of non-typhoid Salmonella infection in Laos. To examine the usefulness of new screening methods for Salmonella using citrus. Methods: Non-typhoidSalmonella infection of person in Lao PDR was studied in this research (2004-2009). The site was Vientiane capital city in 2004. Research from rural villages locating suburb of Vientiane during 2005-2008 was carried out. Rural villages in Attapu province where ethnic minorities were living was searched for this study in 2009. During this research, to detect Salmonella strain, a new method using citrus and citrus extract named MY phenomenon that observing black ring (MIDO ring) on DHL agar was tried. The slice lemon and lime were used for this trial in 2004. After 2005, disk of ascorbic acid and citric acid were used for the device instead of citrus fruits itself. Results: During this research, 65 of 272 human samples (23.9%) were infected with non-typhoid Salmonella. Conclusions: During this study, the method using citrus and citrus extracts was accepted for the detection of Salmonella. This study shows that with citrus and citrus extract, detection of Salmonella is possible using only DHL media. Results suggest that infectious rate of non-typhoid Salmonella was high.

  16. Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan.

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    Luby, S P; Faizan, M K; Fisher-Hoch, S P; Syed, A; Mintz, E D; Bhutta, Z A; McCormick, J B

    1998-03-01

    We conducted a study to evaluate risk factors for developing typhoid fever in a setting where the disease is endemic in Karachi, Pakistan. We enrolled 100 cases with blood culture-confirmed Salmonella typhi between July and October 1994 and 200 age-matched neighbourhood controls. Cases had a median age of 5.8 years. In a conditional logistic regression model, eating ice cream (Odds ratio [OR] = 2.3; 95% confidence interval [CI] 1.2-4.2, attributable risk [AR] = 36%), eating food from a roadside cabin during the summer months (OR = 4.6, 95% CI 1.6-13.0; AR = 18%), taking antimicrobials in the 2 weeks preceding the onset of symptoms (OR = 5.7, 95% CI 2.3-13.9, AR = 21%), and drinking water at the work-site (OR = 44.0, 95% CI 2.8-680, AR = 8%) were all independently associated with typhoid fever. There was no difference in the microbiological water quality of home drinking water between cases and controls. Typhoid fever in Karachi resulted from high-dose exposures from multiple sources with individual susceptibility increased by young age and prior antimicrobial use. Improving commercial food hygiene and decreasing unnecessary antimicrobial use would be expected to decrease the burden of typhoid fever. PMID:9593481

  17. Immune Response to Hepatitis A Vaccine Combined or Given Simultaneously with Typhoid Fever Vaccine.

    Science.gov (United States)

    Vodopija; Baklaic; Vodopija; Clemens

    1997-09-01

    Background: Because both hepatitis A and typhoid vaccination are frequently indicated in the same traveler, a prospective, randomized controlled study was performed to evaluate the feasibility of simultaneous administration of hepatitis A and typhoid fever vaccines in adult volunteers. Methods: Two groups of 25 subjects received either separate injections of hepatitis A (Havrixtrade mark, SmithKline Beecham Biologicals) and typhoid fever (Typhim Vitrade mark, Pasteur-Mérieux) vaccines in opposite arms, or a syringe-mixed combination of both vaccines as a single injection. A booster dose of Havrix was given at 6 months. Results: The immune response to hepatitis A tended to be higher in the mixed-injection group, but this difference was significant (p=.048) only following the booster dose. Adverse reactions were generally mild with no differences between the two groups. Conclusion: A combined formulated vaccine against both typhoid fever and hepatitis A is feasible and offers more convenience without added adverse reactions to travelers who have appropriate indications for both vaccines.

  18. Live Typhoid Vaccine for IBD-Patients—Well Tolerated and with Possible Therapeutic Effect

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    Arnold Berstad

    2008-01-01

    Full Text Available Background: Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD was the incentive of this pilot study.Methods: Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn’s disease with disease activity grade 2–10 on simple colitis index were included in the study. The use of 5-ASA and prednisolone 12.5 mg/day, but no other immunosuppressive drugs, were allowed during the trial. Live typhoid vaccine containing Salmonella serovar Ty21a (Vivotif®, Berna was given in standard doses on day 1, 3 and 5. Symptoms and endoscopic findings were followed up for a 3-months-period.Results: Improvement of abdominal symptoms was recorded in 8 patients after 90 days, one patient was unchanged and one slightly worse. Endoscopic findings improved in 4 patients and were unchanged in 5 patients after 90 days. No side effects were observed.Conclusion: Our results indicate that a live typhoid vaccine is well tolerated by patients with IBD of moderate activity. The symptomatic and endoscopic improvements were not dramatic, but encouraging enough to warrant further studies on the potential therapeutic effect of live typhoid vaccine on patients with IBD.

  19. Live Typhoid Vaccine for IBD-Patients—Well Tolerated and with Possible Therapeutic Effect

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    Gunnar Nysæter

    2008-05-01

    Full Text Available Background: Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD was the incentive of this pilot study. Methods: Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn’s disease with disease activity grade 2–10 on simple colitis index were included in the study. The use of 5-ASA and prednisolone 12.5 mg/day, but no other immunosuppressive drugs, were allowed during the trial. Live typhoid vaccine containing Salmonella serovar Ty21a (Vivotif®, Berna was given in standard doses on day 1, 3 and 5. Symptoms and endoscopic findings were followed up for a 3-months-period. Results: Improvement of abdominal symptoms was recorded in 8 patients after 90 days, one patient was unchanged and one slightly worse. Endoscopic findings improved in 4 patients and were unchanged in 5 patients after 90 days. No side effects were observed. Conclusion: Our results indicate that a live typhoid vaccine is well tolerated by patients with IBD of moderate activity. The symptomatic and endoscopic improvements were not dramatic, but encouraging enough to warrant further studies on the potential therapeutic effect of live typhoid vaccine on patients with IBD.

  20. Typhoid vaccine introduction: An evidence-based pilot implementation project in Nepal and Pakistan.

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    Khan, M Imran; Pach, Alfred; Khan, Ghulam Mustafa; Bajracharya, Deepak; Sahastrabuddhe, Sushant; Bhutta, Waqaas; Tahir, Rehman; Soofi, Sajid; Thapa, Chandra B; Joshi, Nilesh; Puri, Mahesh K; Shrestha, Parisha; Upreti, Shyam Raj; Clemens, John D; Bhutta, Zulfiqar; Ochiai, R Leon

    2015-06-19

    The World Health Organization (WHO) in 2008 recommended the use of currently licensed typhoid vaccines using a high risk or targeted approach. The epidemiology of disease and the vaccine characteristics make school-based vaccination most feasible in reducing typhoid disease burden in many settings. To assess feasibility of school-based typhoid vaccination, two districts in Kathmandu, Nepal and two towns in Karachi, Pakistan were selected for pilot program. Vaccination campaigns were conducted through the departments of health and in partnerships with not-for-profit organizations. In total 257,015 doses of Vi polysaccharide vaccine were given to students in grades 1-10 of participating schools. The vaccination coverage ranged from 39 percent (38,389/99,503) in Gulshan town in Karachi, to 81 percent (62,615/77,341) in Bhaktapur in Kathmandu valley. No serious adverse event was reported post vaccination. The coverage increased for vaccination of the second district in Pakistan as well as in Nepal. There was an initial concern of vaccine safety. However, as the campaign progressed, parents were more comfortable with vaccinating their children in schools. Supported and conducted by departments of health in Pakistan and Nepal, a school-based typhoid vaccination was found to be safe and feasible.

  1. Persistence of antibody titres three years after vaccination with Vi polysaccharide vaccine against typhoid fever.

    Science.gov (United States)

    Tacket, C O; Levine, M M; Robbins, J B

    1988-08-01

    After a single injection of purified Vi polysaccharide vaccine against typhoid fever, serum titres were followed in student volunteers by passive haemagglutination assay and by radioimmunoassay. Elevated Vi antibody titres were still present after 36 months. This preliminary study should be followed by further investigations on the extent and duration of protection provided by Vi vaccine, and on volunteers in endemic areas.

  2. Typhoid fever vaccines: systematic review and meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Fraser, Abigail; Paul, Mical; Goldberg, Elad; Acosta, Camilo J; Leibovici, Leonard

    2007-11-01

    We undertook a systematic review and meta-analysis of randomised controlled trials comparing a typhoid fever vaccine with any alternative typhoid fever vaccine or inactive agent. Trials evaluating killed whole-cell vaccines were excluded. The cumulative efficacy at 3 years for the Ty21a and the polysaccharide Vi vaccine were similar: 51% (95%CI 36%, 62%), and 55% (95%CI 30%, 70%), respectively. The cumulative efficacy of the Vi-rEPA vaccine at 3.8 years was higher, 89% (95%CI 76%, 97%), but this vaccine has not yet been licensed for use and was evaluated in only one trial. Adverse events were mild in nature and for most, not significantly more frequent in any of the vaccine groups when compared with placebo. Both the currently licensed Ty21a and Vi vaccine, are safe and efficacious for preventing typhoid fever. Neither vaccine is currently registered for administration to children below 2 years of age. Given the recent finding that typhoid fever also affects infants, development of a conjugate vaccine is warranted.

  3. The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.

    Science.gov (United States)

    Pham Thanh, Duy; Thompson, Corinne N; Rabaa, Maia A; Sona, Soeng; Sopheary, Sun; Kumar, Varun; Moore, Catrin; Tran Vu Thieu, Nga; Wijedoru, Lalith; Holt, Kathryn E; Wong, Vanessa; Pickard, Derek; Thwaites, Guy E; Day, Nicholas; Dougan, Gordon; Turner, Paul; Parry, Christopher M; Baker, Stephen

    2016-06-01

    Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1-11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines. PMID:27331909

  4. Anti-S. typhi Vi IgG levels in children with and without typhoid vaccinations

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    Sriandayani

    2014-09-01

    Full Text Available Background Typhoid fever is endemic to Indonesia, with an annual incidence of 13/10,000 people. Vaccination has been shown to be an effective method to prevent typhoid fever. Of several vaccine types, the polysaccharide Vi vaccine is the most commonly used typhoid vaccine in developing countries. Results of previous studies remain inconclusive on the necessity of revaccination every 3 years. Objective To compare the mean serum antibody titers of anti-S. typhi Vi IgG and the proportion of children with protective antibody levels between children with and without typhoid Vi vaccination. Methods We conducted a cross-sectional study at Tuminting District, Manado from June to September 2012. Data was analyzed using independent T-test and Fisher’s test. Serum anti-S. typhi Vi IgG levels were measured by enzyme-linked immunosorbent assay (ELISA method. Results Seventy-six subjects were divided into two groups: 38 children who had received the typhoid Vi vaccination more than 3 years prior to this study and 38 children who never had typhoid vaccinations as a control group. No statistically significant difference in age and gender was found between the two groups. The mean serum anti-Vi IgG level was 0.55 ug/mL (SD 0.58; 95%CI 0.36 to 0.74 in the vaccinated group, significantly higher than that of the control group [0.31 ug/mL (SD 0.42; 95%CI 0.17 to 0.44; P=0.038]. The proportion of children with protective anti-Vi antibody level was higher in the vaccinated group (23.7% than in the control group (10.5%, however, this difference was not statistically significant (P=0.128. Conclusion The mean serum anti-S. typhi Vi IgG antibody level in children who had been vaccinated more than 3 years prior to the study is higher than in children who had never received typhoid vaccinations. Nevertheless, the mean antibody titers are generally non-protective in both groups. Also, the proportion of children with protective antibody levels is not significantly different

  5. The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.

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    Duy Pham Thanh

    2016-06-01

    Full Text Available Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1-11.5 years. The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged <15 years were observed over the study period. A population-based risk factor analysis found that access to water within households and increasing distance from Tonle Sap Lake were protective. Spatial mapping and WGS provided additional resolution for these findings, and confirmed that proximity to the lake was associated with discrete spatiotemporal disease clusters. We confirmed the dominance of MDR H58 S. Typhi in this population, and found substantial evidence of diversification (at least seven sublineages within this single lineage. We conclude that there is a substantial burden of pediatric typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines.

  6. Epidemiology of Typhoid Fever in Iran during Last Five Decades from 1962-2011

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    Hossein Masoumi Asl

    2013-01-01

    Full Text Available Background: Typhoid fever is one of the most important infectious diseases transmitted by contaminated food and water. This study aimed at epidemiological features of disease during the last five decades, over the period from 1962-2011.Methods: A retrospective cross-sectional study was conducted using typhoid fever national surveillance data.Results: The highest incidence of typhoid fever was registered in 1965 with 133.4 /100,000 cases/year and the lowest in 2011 with 0.52/100,000 cases/year. Typhoid fever incidence in Iran had three phases. Before the year 1969, with high incidence >100 (phase 1, the period between1969-1996 with medium (10-100, (Phase 2 and the phase 3 has inaugurated from 1996 until now with low incidence rate less than 10 /100,000. Kermanshah Province was the most infected area. Most cases were occurred in warm months in 2010. Of 196 (31% cases were under 15 years old whom were more affected. 53.6% of total cases in 2010 were female and 56.6% stayed in rural area. In 2010, 27.8% cases were confirmed. Among positive cases, the sources of culture were 46.8% stool, 37.2% blood, 14.6% urine and 1.2% bone marrow. Following treatment, 97.8% of cases were recovered completely and in 1.6% of cases had experienced complications and only 0.6% of confirmed cases have been died.Conclusion: As a result of development in socio-economic condition in Iran, the typhoid fever incidence has been dramatically declined from high (133.4/100,000 cases/year in 1965 to low (0.52/100,000 cases/year in 2011.

  7. Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.

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    Date, Kashmira A; Bentsi-Enchill, Adwoa D; Fox, Kimberley K; Abeysinghe, Nihal; Mintz, Eric D; Khan, M Imran; Sahastrabuddhe, Sushant; Hyde, Terri B

    2014-10-01

    Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures. PMID:25275329

  8. The Influence of Drinking Water Access on the Occurrence of Water-borne Diseases (Diarrhea and Typhoid)

    OpenAIRE

    Khadijah Azhar; Ika Dharmayanti; Athena Anwar

    2015-01-01

    Background: Poor and inadequate drinking water supply are the cause of the high occurrence of water-borne diseases,such as diarrhea and typhoid. These diseases often caused an outbreak among the citizens. This article was a furtheranalysis of data obtained from Basic Health Research (Riskesdas) in 2007 with the aim to figure out the influence of drinkingwater access against the occurrence of diarrhea and typhoid. Methods: the used samples were taken from all samples ofthe 2007 Riskesdas, whic...

  9. Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa D; Fox, Kimberley K; Abeysinghe, Nihal; Mintz, Eric D; Khan, M Imran; Sahastrabuddhe, Sushant; Hyde, Terri B

    2014-10-01

    Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures.

  10. DNA extraction columns contaminated with murine sequences.

    Directory of Open Access Journals (Sweden)

    Otto Erlwein

    Full Text Available Sequences of the novel gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV have been described in human prostate cancer tissue, although the amounts of DNA are low. Furthermore, XMRV sequences and polytropic (p murine leukemia viruses (MLVs have been reported in patients with chronic fatigue syndrome (CFS. In assessing the prevalence of XMRV in prostate cancer tissue samples we discovered that eluates from naïve DNA purification columns, when subjected to PCR with primers designed to detect genomic mouse DNA contamination, occasionally gave rise to amplification products. Further PCR analysis, using primers to detect XMRV, revealed sequences derived from XMRV and pMLVs from mouse and human DNA and DNA of unspecified origin. Thus, DNA purification columns can present problems when used to detect minute amounts of DNA targets by highly sensitive amplification techniques.

  11. Serology of Typhoid Fever in an Area of Endemicity and Its Relevance to Diagnosis

    Science.gov (United States)

    House, Deborah; Wain, John; Ho, Vo A.; Diep, To S.; Chinh, Nguyen T.; Bay, Phan V.; Vinh, Ha; Duc, Minh; Parry, Christopher M.; Dougan, Gordon; White, Nicholas J.; Hien, Tran Tinh; Farrar, Jeremy J.

    2001-01-01

    Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of ≥0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P ≤ 0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available

  12. International travel and the risk of hospitalization with non-typhoidal Salmonella bacteremia. A Danish population-based cohort study, 1999-2008

    OpenAIRE

    Mølbak Kåre; Ethelberg Steen; Holt Hanne M; Kristensen Brian; Koch Kristoffer; Schønheyder Henrik C

    2011-01-01

    Abstract Background Information is sparse regarding the association between international travel and hospitalization with non-typhoidal Salmonella bacteremia. The aim of this study was to determine the proportion, risk factors and outcomes of travel-related non-typhoidal Salmonella bacteremia. Methods We conducted a 10-year population-based cohort study of all patients hospitalized with non-typhoidal Salmonella bacteremia in three Danish counties (population 1.6 million). We used denominator ...

  13. The iron link between malaria and invasive non-typhoid Salmonella infections

    OpenAIRE

    van Santen, Susanne; de Mast, Quirijn; Swinkels, Dorine W.; van der Ven, André J. A. M.

    2013-01-01

    Epidemiological studies have demonstrated an association between malaria and invasive non-typhoid Salmonella (NTS) infections, especially in children. We explore the role of iron as a possible co-factor in this association. Malarial disease, among others, is associated with enhanced erythrophagocytosis and inflammation, which increases the iron content of macrophages and thereby also the survival of Salmonellae spp within macrophages. Whether iron supplementation programs augment the risk of ...

  14. Evaluation of fliC-d based direct blood PCR assays for typhoid diagnosis

    OpenAIRE

    Das, Surojit; Ray, Ujjwayini; Akhter, Irfaan; Chattopadhyay, Arka; Paul, Dilip Kumar; Dutta, Shanta

    2016-01-01

    Background Typhoid cases need to be diagnosed accurately for early antibiotic therapy and reducing mortality. Identification of Salmonella Typhi (S. Typhi) in blood culture is conclusive, but has poor sensitivity. Detection of S. Typhi by PCR from blood sample has shown promise. Real-time quantitative PCR (Q-PCR) has been widely used in diagnostics for its rapidity and reliability. In the present study, the performance of molecular methods like conventional PCR (C-PCR), nested PCR (N-PCR) and...

  15. Serology of Typhoid Fever in an Area of Endemicity and Its Relevance to Diagnosis

    OpenAIRE

    House, Deborah; Wain, John; Ho, Vo A.; To S. Diep; Chinh, Nguyen T.; Bay, Phan V.; Vinh, Ha; Duc, Minh; Parry, Christopher M.; Dougan, Gordon; White, Nicholas J.; Hien, Tran Tinh; Farrar, Jeremy J.

    2001-01-01

    Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam i...

  16. Non-typhoidal Salmonella and Campylobacter infections among HIV-positive patients in Denmark

    DEFF Research Database (Denmark)

    Larsen, I.K.; Gradel, Kim Oren; Helms, M.;

    2011-01-01

    Non-typhoidal Salmonella (NTS) and Campylobacter are common causes of diarrhoea in human immunodeficiency virus (HIV)-positive patients. To investigate if incidence has changed since the introduction of highly active antiretroviral therapy (HAART), we combined data from The Danish Surveillance Re...... population. Moreover our study suggests that there is an increased incidence of Campylobacter-related illness among homosexual men in the HIV-positive population....

  17. Surgical treatment of peritonitis due to typhoid fever in a Hospital in Mozambique

    Directory of Open Access Journals (Sweden)

    Arnulfo Gallego Mariño

    2015-07-01

    Full Text Available Background: Typhoid fever is a cause of peritonitis by perforation of the intestinal loops and provokes the death of many people; therefore it constitutes a health problem in Mozambique.Objective: To describe the patients operated on, with the diagnosis of peritonitis resulting from typhoid fever, at the surgery department of the Provincial Hospital in Quelimane, Zambezia Province, Mozambique, from November 1, 2011 to April 30, 2012.Methods: A descriptive study of the patients operated on with the diagnosis of peritonitis resulting from typhoid fever, at the hospital and period herein mentioned, was performed. The study population consisted of 96 patients who were operated on. The variables that were measured were: age, sex, onset of symptoms, total perforations, performed surgical treatment and complications.Results: Male patients of the 25 to 50 age group prevailed; most of them visited the service after 72 hours of the onset of symptoms; in 66 patients only one perforation was found and the surgical procedure mostly used was the suture of the perforation and the washout of the abdominal cavity.Conclusions: Most of the patients visited the service 72 hours after the onset of symptoms; they underwent surgery; and wound infection was the most frequent complication.

  18. In Vitro intestinal mucosal epithelial responses to wild-typeSalmonella Typhi and attenuated typhoid vaccines

    Directory of Open Access Journals (Sweden)

    Maria eFiorentino

    2013-02-01

    Full Text Available Typhoid fever, caused by S. Typhi, is responsible for approximately 200,000 deaths per year worldwide. Little information is available regarding epithelium-bacterial interactions in S. Typhi infection. We have evaluated in vitro the effects of wild-type S. Typhi, the licensed Ty21a typhoid vaccine and the leading strains CVD 908-htrA and CVD 909 vaccine candidates on intestinal barrier function and immune response. Caco2 monolayers infected with wild-type S. Typhi exhibited alterations in the organization of tight junctions, increased paracellular permeability, and a rapid decrease in Trans-Epithelial Electrical Resistance as early as 4h post-exposure. S. Typhi triggered the secretion of interleukin (IL-8 and IL-6. Caco2 cells infected with the attenuated strains exhibited a milder pro-inflammatory response with minimal disruption of the barrier integrity. We conclude that wild-type S. Typhi causes marked transient alterations of the intestinal mucosa that are more pronounced than those observed with Ty21a or new generation attenuated typhoid vaccine candidates.

  19. Reassessment of frequency of occurrence of typhoid fever and cost efficacy analysis of antibiotic therapy.

    Science.gov (United States)

    Sridhar, C B; Kulkarni, R D

    1995-10-01

    Typhoid fever has assumed importance due to the increased incidence of drug resistance in India. The exact magnitude of the problem is not accurately known. The objective of this study was to collect retrospectively the data on the incidence and frequency of typhoid fever among hospital admissions at St. Johns Medical College Hospital (SJMCH), Bangalore during the year 1987 to 1992 and also to study the sensitivity pattern and the use of antibiotics. The study was also aimed at comparison of immunogenicity and tolerance of conventional vaccine to the newer polysaccharide vaccine. It was found that the incidence of typhoid fever showed change from epidemic to endemic situation with outbreaks of epidemics. Sensitivity pattern also showed change during the same period and antibiotic resistance was increasingly demonstrated from 1989. Cost per patient and total cost to the hospital due to increased admissions also showed progressive increase. The polysaccharide vaccine (recently made available in India) had very low adverse reaction profile with higher immunogenicity as compared to conventional vaccine. Its single dose effect with long lasting immunity indicates it probable usefulness in the eradication of disease.

  20. Efficacy and safety of azithromycin for uncomplicated typhoid fever: an open label non-comparative study.

    Science.gov (United States)

    Aggarwal, Anju; Ghosh, Apurba; Gomber, Sunil; Mitra, Monjori; Parikh, A O

    2011-07-01

    An open-labelled, non-comparative study was conducted in 117 children aged 2-12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study.Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever. PMID:21555791

  1. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

    DEFF Research Database (Denmark)

    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S....... In the current study genetic adaptation during experimental chronic S. Typhimurium infections of mice, an established model of chronic typhoid fever, was probed as an approach for studying the molecular mechanisms of host-adaptation during long-term host-association. Results Individually sequence-tagged wild......, the kdgR-SNP was confirmed to confer selective advantage during chronic infections and constitute a true patho-adaptive mutation. Together, the results provide evidence for rapid genetic adaptation to the host of S. Typhimurium and validate experimental evolution in the context of host infection...

  2. High-resolution genotyping of the endemic Salmonella Typhi population during a Vi (typhoid vaccination trial in Kolkata.

    Directory of Open Access Journals (Sweden)

    Kathryn E Holt

    2012-01-01

    Full Text Available BACKGROUND: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi, is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas. METHODOLOGY: We used single nucleotide polymorphism (SNP typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003-December 2006, vaccinations given December 2004. PRINCIPAL FINDINGS: A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%, which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole. Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin. Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes. CONCLUSIONS: Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period.

  3. Validation of the Dri-Dot Latex agglutination and IgM lateral flow assays for the diagnosis of typhoid fever in an Egyptian population

    NARCIS (Netherlands)

    I. Nakhla; H. El Mohammady; A. Mansour; J.D. Klena; K. Hassan; Y. Sultan; R. Pastoor; T.H. Abdoel; H. Smits

    2011-01-01

    Laboratory confirmation of typhoid fever is essential for appropriate medical treatment. Blood culture is a standard test for diagnosis of typhoid fever, but well-equipped diagnostic facilities to perform culture are seldom available in endemic areas. We retrospectively compared 2 diagnostic field t

  4. Current status and prospects of typhoid vaccines%伤寒疫苗的现状及展望

    Institute of Scientific and Technical Information of China (English)

    潘殊男

    2011-01-01

    Typhoid fever is still a major public health problem in developing countries.Vaccination is the most effective measure to control typhoid fever.This article describes safety and efficacy of early and current typhoid vaccines,and discusses current status of development and research and application prospects of Salmonella typhi Vi polysaccharide conjugate vaccine.%伤寒仍是发展中国家的主要公共卫生问题,控制伤寒的最有效措施是接种疫苗.此文介绍了早期伤寒疫苗和现行伤寒疫苗的的安全性和有效性,讨论了伤寒Vi多糖结合疫苗的研发现状及应用前景.

  5. Typhoid outbreak in Songkhla, Thailand 2009-2011: clinical outcomes, susceptibility patterns, and reliability of serology tests.

    Directory of Open Access Journals (Sweden)

    Wannee Limpitikul

    Full Text Available OBJECTIVE: To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009-2011 typhoid outbreak in Songkhla province in Thailand. METHOD: The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin, were evaluated. RESULTS: S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7-14 days. The median time (IQR of fever before treatment and duration of fever after treatment were 5 (4, 7 days and 4 (3, 5 days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%, and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively. CONCLUSION: Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.

  6. Low-level quinolone-resistance in multi-drug resistant typhoid

    International Nuclear Information System (INIS)

    To find out the frequency of low-level quinolone-resistance in Multi-Drug Resistant (MDR) typhoid using nalidixic acid screening disc. Blood was obtained from suspected cases of typhoid fever and cultured in to BacT/ALERT. The positive blood cultures bottles were subcultured. The isolates were identified by colony morphology and biochemical tests using API-20E galleries. Susceptibility testing of isolates was done by modified Kirby-Bauer disc diffusion method on Muellar Hinton Agar. For the isolates, which were resistant to nalidixic acid by disc diffusion method, Minimal Inhibitory Concentrations (MICs) of ciprofloxacin and nalidixic acid were determined by using the E-test strips. Disc diffusion susceptibility tests and MICs were interpreted according to the guidelines provided by National Committee for Control Laboratory Standard (NCCLS). A total of 21(65.5%) out of 32 isolates of Salmonellae were nalidixic acid-resistant by disk diffusion method. All the nalidixic acid-resistant isolates by disc diffusion method were confirmed by MICs for both ciprofloxacin and nalidixic acid. All the nalidixic acid-resistant isolates had a ciprofloxacin MIC of 0.25-1 microg/ml (reduced susceptibility) and nalidixic acid MICs > 32 microg (resistant). Out of all Salmonella isolates, 24 (75%) were found to be MDR, and all were S. typbi. Low-level quinolone-resistance in typhoid was high in this small series. Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a reliable and cost-effective method to detect low-level fluoroquinolone resistance, especially in the developing countries. (author)

  7. Comparisons of predictors for typhoid and paratyphoid fever in Kolkata, India

    Directory of Open Access Journals (Sweden)

    Deen Jacqueline L

    2007-10-01

    Full Text Available Abstract Background: Exposure of the individual to contaminated food or water correlates closely with the risk for enteric fever. Since public health interventions such as water improvement or vaccination campaigns are implemented for groups of individuals we were interested whether risk factors not only for the individual but for households, neighbourhoods and larger areas can be recognised? Methods: We conducted a large enteric fever surveillance study and analyzed factors which correlate with enteric fever on an individual level and factors associated with high and low risk areas with enteric fever incidence. Individual level data were linked to a population based geographic information systems. Individual and household level variables were fitted in Generalized Estimating Equations (GEE with the logit link function to take into account the likelihood that household factors correlated within household members. Results: Over a 12-month period 80 typhoid fever cases and 47 paratyphoid fever cases were detected among 56,946 residents in two bustees (slums of Kolkata, India. The incidence of paratyphoid fever was lower (0.8/1000/year, and the mean age of paratyphoid patients was older (17.1 years than for typhoid fever (incidence 1.4/1000/year, mean age 14.7 years. Residents in areas with a high risk for typhoid fever had lower literacy rates and economic status, bigger household size, and resided closer to waterbodies and study treatment centers than residents in low risk areas. Conclusion: There was a close correlation between the characteristics detected based on individual cases and characteristics associated with high incidence areas. Because the comparison of risk factors of populations living in high versus low risk areas is statistically very powerful this methodology holds promise to detect risk factors associated with diseases using geographic information systems.

  8. Risk factors for typhoid outbreak in Sungai Congkak Recreational Park, Selangor 2009.

    Science.gov (United States)

    Anita, S; Amir, K M; Fadzilah, K; Ahamad, J; Noorhaida, U; Marina, K; Paid, M Y; Hanif, Z

    2012-02-01

    Typhoid fever continues to pose public health problems in Selangor where cases are found sporadically with occasional outbreaks reported. In February 2009, Hospital Tengku Ampuan Rahimah (HTAR) reported a cluster of typhoid fever among four children in the pediatric ward. We investigated the source of the outbreak, risk factors for the infection to propose control measures. We conducted a case-control study to identify the risk factors for the outbreak. A case was defined as a person with S. typhi isolated from blood, urine or stool and had visited Sungai Congkak recreational park on 27th January 2010. Controls were healthy household members of cases who have similar exposure but no isolation of S. typhi in blood, urine or stool. Cases were identified from routine surveillance system, medical record searching from the nearest clinic and contact tracing other than family members including food handlers and construction workers in the recreational park. Immediate control measures were initiated and followed up. Twelve (12) cases were identified from routine surveillance with 75 household controls. The Case-control study showed cases were 17 times more likely to be 12 years or younger (95% CI: 2.10, 137.86) and 13 times more likely to have ingested river water accidentally during swimming (95% CI: 3.07, 58.71). River water was found contaminated with sewage disposal from two public toilets which effluent grew salmonella spp. The typhoid outbreak in Sungai Congkak recreational park resulted from contaminated river water due to poor sanitation. Children who accidentally ingested river water were highly susceptible. Immediate closure and upgrading of public toilet has stopped the outbreak. PMID:22582542

  9. Updated recommendations for the use of typhoid vaccine--Advisory Committee on Immunization Practices, United States, 2015.

    Science.gov (United States)

    Jackson, Brendan R; Iqbal, Shahed; Mahon, Barbara

    2015-03-27

    These revised recommendations of the Advisory Committee on Immunization Practices update recommendations published in MMWR in 1994 and include updated information on the two currently available vaccines and on vaccine safety. They also include an update on the epidemiology of enteric fever in the United States, focusing on increasing drug resistance in Salmonella enterica serotype Typhi, the cause of typhoid fever, as well as the emergence of Salmonella serotype Paratyphi A, a cause of paratyphoid fever, against which typhoid vaccines offer little or no protection.

  10. Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG12D/Pdx-1-Cre Mice

    OpenAIRE

    Liao, Jie; Hwang, Sung Hee; Li, Haonan; Liu, Jun-Yan; Hammock, Bruce D.; Yang, Guang-Yu

    2016-01-01

    Mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. In the process of long-standing chronic inflammation, aberrant metabolites of arachidonic acid play a crucial role in promoting carcinogenesis, in which the soluble epoxide hydrolase (sEH), as a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we determined the effect ...

  11. IDENTIFICATION AND ANTIMICROBIAL SUSCEPTIBILITY OF SALMONELLA GALLINARUM ISOLATED FROM FOWL TYPHOID OUTBREAK IN BACKYARD VANARAJA FOWL

    Directory of Open Access Journals (Sweden)

    S. Dey

    2016-06-01

    Full Text Available From a disease outbreak among Vanaraja fowl, an indigenous Indian Breed reared by backyard system in Jhargram, West Bengal, Salmonella Gallinarum was isolated and characterised. The outbreak occurred among 6-8 day old chicks. A total of 150 birds died in a span of 5 days. Salmonella Gallinarum were identified and confirmed by standard bacteriological methods and presence of invasion ( invA gene was detected by PCR. The isolates were susceptible to 15 common antimicrobials in vitro. Although chemotherapy may be effective, outbreaks of fowl typhoid in backyard poultry warranted precise control policy

  12. Non-Typhoidal Salmonella Gastroenteritis at a Diarrheal Hospital in Dhaka, Bangladesh, 1996–2011

    OpenAIRE

    Leung, Daniel T; Sumon K Das; Malek, M.A.; Ahmed, Dilruba; Khanam, Farhana; Qadri, Firdausi; Faruque, A. S. G.; Ryan, Edward T.

    2013-01-01

    Data on non-typhoidal Salmonella (NTS) infection in South Asia are limited. We used data gathered prospectively from 1996 to 2011 as part of a hospital surveillance system in Dhaka, Bangladesh, to identify diarrheal patients with NTS isolated from stool. NTS was isolated in 1.3% (468 of 37,439) of diarrheal patients; 47% of total cases of NTS were in children < 5 years of age, although older adults (≥ 60 years) had the highest isolation rates. NTS isolation peaked in the monsoon months of Jul...

  13. Non-typhoid Salmonella bacteraemia in Greater Copenhagen 1984 to 1988

    DEFF Research Database (Denmark)

    Lester, Anne; Eriksen, N H; Nielsen, H;

    1991-01-01

    A retrospective survey of non-typhoid Salmonella bacteraemia in the period 1984 to 1988 was carried out by the five departments of clinical microbiology in Greater Copenhagen. A total of 168 patients were identified. A gradual increase was observed from 11 cases in 1984 to 58 cases in 1988....... The corresponding incidence per 100,000 inhabitants in Copenhagen rose from 0.9 in 1984 to 5.0 in 1988. During the same period the total registered incidence of human Salmonella infections in Denmark increased from 17.6 to 67.4 per 100,000 inhabitants. The serotype most often isolated from bacteraemic patients...

  14. Mary Mallon (1869-1938) and the history of typhoid fever.

    Science.gov (United States)

    Marineli, Filio; Tsoucalas, Gregory; Karamanou, Marianna; Androutsos, George

    2013-01-01

    Mary Mallon was born in 1869 in Ireland and emigrated to the US in 1884. She had worked in a variety of domestic positions for wealthy families prior to settling into her career as a cook. As a healthy carrier of Salmonella typhi her nickname of "Typhoid Mary" had become synonymous with the spread of disease, as many were infected due to her denial of being ill. She was forced into quarantine on two separate occasions on North Brother Island for a total of 26 years and died alone without friends, having evidently found consolation in her religion to which she gave her faith and loyalty. PMID:24714738

  15. Evaluation of a new Vi polysaccharide typhoid vaccine in children aged 2-5 years.

    Science.gov (United States)

    Cordero-Yap, L; Rivera, R G; Dispo, A P; Mallabo, J

    2001-01-01

    Typhoid fever is a major cause of morbidity and mortality in many parts of the world. In view of the increasing resistance of Salmonella typhi against antibiotics and the high costs associated with improving sanitation conditions, vaccination programs would be of great benefit. We report on the evaluation of a new candidate VI (sic) polysaccharide typhoid vaccine (TypheriX (sic), SmithKline Beecham Pharmaceuticals), tested in Filipino children aged 2-5 years where the profile was compared with that of a competitor-vaccine (Typhim (sic), Pasteur Merieux Connaught). Vaccination with the new candidate vaccine was followed by fewer general symptoms (2.9%) than with the competitor vaccine (14.1%), particularly with lower incidence of fever. The new candidate vaccine is also highly immunogenic: >99% of the vacinees were immune 28 days post vaccination with comparable GMTs of 3597 EL.U/ml for TypheriX (sic) and 3365 EL.U/ml for Typhim (sic). This trial shows that the available VI (sic) polysaccharide vaccines provide a reliable means in preventing a disease responsible for a significant morbidity and placing a heavy burden on health budgets.

  16. Challenges and Opportunities for Typhoid Fever Control: A Call for Coordinated Action.

    Science.gov (United States)

    Steele, A Duncan; Hay Burgess, Deborah C; Diaz, Zoey; Carey, Megan E; Zaidi, Anita K M

    2016-03-15

    The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines.

  17. Investigation of the response to the enterobacterial common antigen after typhoid vaccination

    Directory of Open Access Journals (Sweden)

    Arlete M. Milhomem

    1987-03-01

    Full Text Available Antibodies against the Salmonella typhi enterobacterial common antigen (ECA and the O and H antigens were investigated in sera from healthy male subjects who had been previously vaccinated with the typhoid vaccine. No serological response to ECA was observed. Sera from subjects not previously vaccinated presented titers of ECA hemagglutinins which quantitatively were related to the presence ofH titers, but not to O agglutinins but with no statistical significance. The results are discussed in relation to the possible protective immunological mechanisms in typhoid fever.Anticorpos contra o antígeno comum de enterobactérias (ECA bem como contra os antigenos somáticos (O e flagelar (H de Salmonella typhi foram investigados no soro de recrutas do sexo masculino, após a vacinação. Não fo i detectada resposta humoral para ECA. Os soros obtidos antes da vacinação mostraram hemaglutininas para ECA acompanhando a presença de aglutininas para o antígeno H, ao contrário do que se observou em relação ao antígeno O. Discutem-se os resultados quanto ao possível mecanismo da imunoproteção da febre tifóide.

  18. Spatiotemporal transmission and determinants of typhoid and paratyphoid fever in Hongta District, Yunnan Province, China.

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    Jin-Feng Wang

    Full Text Available BACKGROUND: Typhoid and paratyphoid fever are endemic in Hongta District and their prevalence, at 113 per 100,000 individuals, remains the highest in China. However, the exact sources of the disease and its main epidemiological characteristics have not yet been clearly identified. METHODS AND FINDINGS: Numbers of typhoid and paratyphoid cases per day during the period 2006 to 2010 were obtained from the Chinese Center of Disease Control (CDC. A number of suspected disease determinants (or their proxies, were considered for use in spatiotemporal analysis: these included locations of discharge canals and food markets, as well as socio-economic and environmental factors. Results showed that disease prevalence was spatially clustered with clusters decreasing with increasing distance from markets and discharge canals. More than half of the spatial variance could be explained by a combination of economic conditions and availability of health facilities. Temporal prevalence fluctuations were positively associated with the monthly precipitation series. Polluted hospital and residential wastewater was being discharged into rainwater canals. Salmonella bacteria were found in canal water, on farmland and on vegetables sold in markets. CONCLUSION: DISEASE TRANSMISSION IN HONGTA DISTRICT IS DRIVEN PRINCIPALLY BY TWO SPATIOTEMPORALLY COUPLED CYCLES: one involving seasonal variations and the other the distribution of polluted farmland (where vegetables are grown and sold in markets. Disease transmission was exacerbated by the fact that rainwater canals were being used for disposal of polluted waste from hospitals and residential areas. Social factors and their interactions also played a significant role in disease transmission.

  19. Treatment cost for typhoid fever at two hospitals in Kolkata, India.

    Science.gov (United States)

    Sur, Dipika; Chatterjee, Susmita; Riewpaiboon, Arthorn; Manna, Byomkesh; Kanungo, Suman; Bhattacharya, Sujit K

    2009-12-01

    The purpose of this study was to estimate treatment cost for typhoid fever at two hospitals in Kolkata, India. This study was an incidence-based cost-of-illness analysis from the providers' perspective. Micro-costing approach was employed for calculating patient-specific data. Unit costs of medical services used in the calculation were directly measured from the study hospital by standard method. The study hospitals were selected based on accessibility to data and cooperation. Eighty-three Widal-positive and/or culture-confirmed patients with typhoid fever during November 2003-April 2006 were included in the study. Most (93%) patients were children. Eighty-one percent was treated at the outpatient department. The average duration of hospitalization for child and adult patients was 8.4 and 4.2 days respectively. The average cost of treating children, adults, and all patients was US$ 16.72, 72.71, and 20.77 respectively (in 2004 prices). Recalculation based on 80% occupancy rate in inpatient wards (following the recommendation of the World Health Organization) found that the cost of treating children, adults, and all patients was US$ 14.53, 36.44, and 16.11 respectively.

  20. Antibiotic resistance, integrons and Salmonella genomic island 1 among non-typhoidal Salmonella serovars in The Netherlands.

    NARCIS (Netherlands)

    Vo, An T T; Duijkeren, Engeline van; Fluit, Ad C; Wannet, Wim J B; Verbruggen, Anjo J; Maas, Henny M E; Gaastra, Wim

    2006-01-01

    The objective of this study was to investigate the antimicrobial resistance patterns, integron characteristics and gene cassettes as well as the presence of Salmonella genomic island 1 (SGI1) in non-typhoidal Salmonella (NTS) isolates from human and animal origin. Epidemiologically unrelated Dutch N

  1. Rapid diagnosis of typhoid fever by enzyme-linked immunosorbent assay detection of Salmonella serotype typhi antigens in urine.

    Science.gov (United States)

    Fadeel, Moustafa Abdel; Crump, John A; Mahoney, Frank J; Nakhla, Isabelle A; Mansour, Adel M; Reyad, Baheia; El Melegi, Dawlat; Sultan, Yehia; Mintz, Eric D; Bibb, William F

    2004-03-01

    We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies to capture somatic antigen 9 (O9), flagellar antigen d (Hd), and the Vi capsular polysaccharide antigen (Vi) from the urine of persons with and without typhoid fever. Sequential urine samples were collected from 44 patients with blood culture-confirmed typhoid fever and from two control groups. The first control group included patients with brucellosis (n = 12) and those with clinically diagnosed, non-typhoid, acute, febrile illness (n = 27). The second control group was a sample of healthy volunteer laboratory workers (n = 11). When assessed relative to date of fever onset, sensitivity was highest during the first week for all three antigens: Vi was detected in the urine of nine (100%) patients, O9 in 4 (44%) patients, and Hd in 4 (44%) patients. Sequential testing of two urine samples from the same patient improved test sensitivity. Combined testing for Vi with O9 and Hd produced a trend towards increased sensitivity without compromising specificity. The specificity for Vi exceeded 90% when assessed among both febrile and healthy control subjects, but was only 25% when assessed among patients with brucellosis. Detection of urinary Vi antigen with this ELISA shows promise for the diagnosis of typhoid fever, particularly when used within the first week after fever onset. However, positive reactions for Vi antigen in patients with brucellosis must be understood before urinary Vi antigen detection can be developed further as a useful rapid diagnostic test.

  2. Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans.

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    Thomas C Darton

    2015-09-01

    Full Text Available Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge.Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP, and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia.We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi.

  3. A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference.

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    Helen L Storey

    Full Text Available Novel typhoid diagnostics currently under development have the potential to improve clinical care, surveillance, and the disease burden estimates that support vaccine introduction. Blood culture is most often used as the reference method to evaluate the accuracy of new typhoid tests; however, it is recognized to be an imperfect gold standard. If no single gold standard test exists, use of a composite reference standard (CRS can improve estimation of diagnostic accuracy. Numerous studies have used a CRS to evaluate new typhoid diagnostics; however, there is no consensus on an appropriate CRS. In order to evaluate existing tests for use as a reference test or inclusion in a CRS, we performed a systematic review of the typhoid literature to include all index/reference test combinations observed. We described the landscape of comparisons performed, showed results of a meta-analysis on the accuracy of the more common combinations, and evaluated sources of variability based on study quality. This wide-ranging meta-analysis suggests that no single test has sufficiently good performance but some existing diagnostics may be useful as part of a CRS. Additionally, based on findings from the meta-analysis and a constructed numerical example demonstrating the use of CRS, we proposed necessary criteria and potential components of a typhoid CRS to guide future recommendations. Agreement and adoption by all investigators of a standardized CRS is requisite, and would improve comparison of new diagnostics across independent studies, leading to the identification of a better reference test and improved confidence in prevalence estimates.

  4. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report.

    Science.gov (United States)

    Acharya, I L; Lowe, C U; Thapa, R; Gurubacharya, V L; Shrestha, M B; Cadoz, M; Schulz, D; Armand, J; Bryla, D A; Trollfors, B

    1987-10-29

    We conducted a pilot study followed by a large clinical trial in Nepal of the use of the capsular polysaccharide of Salmonella typhi (Vi) as a vaccine to prevent typhoid fever. In the pilot study, involving 274 Nepalese, there were no significant side effects of the Vi vaccine; about 75 percent responded with a rise in serum antibodies of fourfold or more. In the clinical trial, residents of five villages were given intramuscular injections of either Vi or, as a control, pneumococcus vaccine dispensed in coded, randomly arranged, single-dose syringes. There were 6907 participants, of whom 6438 were members of the target population (5 to 44 years of age); each was visited every two days. Those with temperatures of 37.8 degrees C or higher for three consecutive days were examined and asked to give blood for culture. Typhoid was diagnosed as either blood culture-positive or clinically suspected on the basis of bradycardia, splenomegaly, and fever, with a negative blood culture. Seventeen months after vaccination, the codes were broken for the 71 patients meeting the criteria for either culture-positive or clinically suspected typhoid. The attack rate of typhoid was 16.2 per 1000 among the controls and 4.1 per 1000 among those immunized with Vi (P less than 0.00001). The efficacy of Vi was 72 percent in the culture-positive cases, 80 percent in the clinically suspected cases, and 75 percent in the two groups combined. These data provide evidence that Vi antibodies confer protection against typhoid. Surveillance continues to determine the duration of Vi-induced immunity.

  5. Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG¹²D/Pdx-1-Cre Mice.

    Science.gov (United States)

    Liao, Jie; Hwang, Sung Hee; Li, Haonan; Liu, Jun-Yan; Hammock, Bruce D; Yang, Guang-Yu

    2016-01-01

    Mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. In the process of long-standing chronic inflammation, aberrant metabolites of arachidonic acid play a crucial role in promoting carcinogenesis, in which the soluble epoxide hydrolase (sEH), as a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we determined the effect of our newly-synthesized novel compound trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM), a dual inhibitor of sEH and RAF1 proto-oncogene serine/threonine kinase (c-RAF), on inhibiting the development of pancreatitis and pancreatic intraepithelial neoplasia (mPanIN) in LSL-Kras(G12D)/Pdx1-Cre mice. The results showed that t-CUPM significantly reduced the severity of chronic pancreatitis, as measured by the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high-grade mPanIN II/III was significantly suppressed. Inhibition of mutant Kras-transmitted phosphorylation of mitogen-activated protein kinase's kinase/extracellular signal-regulated kinases was demonstrated in pancreatic tissues by western blots. Quantitative real-time polymerase chain reaction analysis revealed that t-CUPM treatment significantly reduced the levels of inflammatory cytokines including tumor necrosis facor-α, monocyte chemoattractant protein-1, as well as vascular adhesion molecule-1, and the levels of Sonic hedgehog and Gli transcription factor (Hedgehog pathway). Analysis of the eicosanoid profile revealed a significant increase of the EETs/dihydroxyeicosatrienoic acids ratio, which further confirmed sEH inhibition by t-CUPM. These results indicate that simultaneous inhibition of sEH and c-RAF by t-CUPM is important in preventing chronic pancreatitis and carcinogenesis

  6. Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG¹²D/Pdx-1-Cre Mice.

    Science.gov (United States)

    Liao, Jie; Hwang, Sung Hee; Li, Haonan; Liu, Jun-Yan; Hammock, Bruce D; Yang, Guang-Yu

    2016-01-01

    Mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. In the process of long-standing chronic inflammation, aberrant metabolites of arachidonic acid play a crucial role in promoting carcinogenesis, in which the soluble epoxide hydrolase (sEH), as a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we determined the effect of our newly-synthesized novel compound trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM), a dual inhibitor of sEH and RAF1 proto-oncogene serine/threonine kinase (c-RAF), on inhibiting the development of pancreatitis and pancreatic intraepithelial neoplasia (mPanIN) in LSL-Kras(G12D)/Pdx1-Cre mice. The results showed that t-CUPM significantly reduced the severity of chronic pancreatitis, as measured by the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high-grade mPanIN II/III was significantly suppressed. Inhibition of mutant Kras-transmitted phosphorylation of mitogen-activated protein kinase's kinase/extracellular signal-regulated kinases was demonstrated in pancreatic tissues by western blots. Quantitative real-time polymerase chain reaction analysis revealed that t-CUPM treatment significantly reduced the levels of inflammatory cytokines including tumor necrosis facor-α, monocyte chemoattractant protein-1, as well as vascular adhesion molecule-1, and the levels of Sonic hedgehog and Gli transcription factor (Hedgehog pathway). Analysis of the eicosanoid profile revealed a significant increase of the EETs/dihydroxyeicosatrienoic acids ratio, which further confirmed sEH inhibition by t-CUPM. These results indicate that simultaneous inhibition of sEH and c-RAF by t-CUPM is important in preventing chronic pancreatitis and carcinogenesis.

  7. Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

    Directory of Open Access Journals (Sweden)

    Farhana Khanam

    2015-04-01

    Full Text Available Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains.As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest during acute typhoid fever in adults. We similarly assessed membrane preparation (MP IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years with those seen in older children (6-17 years, adults (18-59 years, and age-matched healthy controls.We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid.This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest

  8. Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report

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    Rashid Abbas

    2010-06-01

    Full Text Available Abstract Introduction We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. Case presentation As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Conclusion Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever.

  9. Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide.

    Science.gov (United States)

    Davies, D Huw; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskis, Algis; Supnet, Medalyn; Felgner, Philip L; Teng, Andy; Pablo, Jozelyn; Molina, Douglas M; Obaro, Stephen K

    2016-08-01

    Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger "hits," whereas the profile in U.S. adults was NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease. PMID:27215295

  10. Working Group on quality, safety and efficacy of typhoid Vi capsular polysaccharide conjugate, vaccines, Jeju, Republic of Korea, 5-7 September 2012.

    Science.gov (United States)

    Jones, Chris; Lee, Chung Keel; Ahn, Chiyoung; Shin, Jinho; Knezevic, Ivana

    2013-09-23

    Typhoid fever is a gastrointestinal disease transmitted through the ingestion of contaminated water or food. The bacterium, Salmonella enterica subspecies enterica serovar Typhi is an important cause of illness and death in many poor countries where access to safe water and basic sanitation is limited. Humans are the only natural host and reservoir of S. Typhi. Typhoid fever causes around 21 million cases and at least 200,000 deaths per year. Currently, several groups are developing typhoid conjugate vaccines that are expected to be safe and effective in infancy or early childhood. The World Health Organization convened a meeting, in collaboration with the Korea Food and Drug Administration, with experts group in September 2012 to develop guidelines for regulatory evaluation of the quality, safety and efficacy of typhoid conjugate vaccines. This report summarizes collective views on scientific and technical issues that need to be considered in the guidelines.

  11. Using next generation sequencing to tackle non-typhoidal Salmonella infections

    DEFF Research Database (Denmark)

    Wain, John; Keddy, Karen H.; Hendriksen, Rene S.;

    2013-01-01

    Africa appears to be human-to-human spread and the association with invasive disease almost absolute, more needs to be done to exclude the possibility of animal reservoirs and to transfer the ability to track all Salmonella infections to the laboratories in the front line. In this mini-review we...... summarise what is currently known about non-typhoidal Salmonella in sub-Saharan Africa and discuss some of the issues which remain.......The publication of studies using next generation sequencing to analyse large numbers of bacterial isolates from global epidemics is transforming microbiology, epidemiology and public health. The emergence of multidrug resistant Salmonella Typhimurium ST313 is one example. While the epidemiology in...

  12. Typhim Vi vaccine against typhoid fever: a clinical trial in Kenya.

    Science.gov (United States)

    Mirza, N B; Wamola, I A; Estambale, B A; Mbithi, E; Poillet, M

    1995-03-01

    Safety, tolerance and immunogenicity of the purified Vi polysaccharide vaccine (Typhim Vi) against typhoid fever was evaluated in primary school children aged 5-15 years. A total of 435 children were vaccinated, each with a single intramuscular injection in the left deltoid muscle. One hundred and ten children were randomly selected for blood samples on day 0 (pre vaccination) and day 30 (post vaccination). Vi antibodies studied by Radio immuno assay (RIA) on 97(88%) paired sera showed a seroconversion rate of 76.2% and seroprotection rate after vaccination was 74.2%, while 6.2% of children already had protective immunity before vaccination. The vaccine was well tolerated. Most commonly reported reactions were mild pain at site of injection (83%), and a few complained of mild swelling (4.6%), induration (1.1%), itching (1.1%) and headaches (1.4%). All reactions were of mild severity and disappeared within 24 to 48 hours.

  13. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  14. Aqueous Extract of Gumiganghwal-tang, a Traditional Herbal Medicine, Reduces Pulmonary Fibrosis by Transforming Growth Factor-β1/Smad Signaling Pathway in Murine Model of Chronic Asthma

    Science.gov (United States)

    Shin, In-Sik; Shin, Hyeun-Kyoo; Jin, Seong Eun; Lee, Mee-Young

    2016-01-01

    Gumiganghwal-tang is a traditional herbal prescription that is used widely for the treatment of the common cold and inflammatory diseases in Korea and other Asian countries. In this study, we investigated the protective effects of a Gumiganghwal-tang aqueous extract (GGTA) against airway inflammation and pulmonary fibrosis using a mouse model of chronic asthma. Chronic asthma was modeled in BALB/c mice via sensitization/challenge with an intraperitoneal injection of 1% ovalbumin (OVA) and inhalation of nebulized 1% OVA for 4 weeks. GGTA (100 mg/kg or 200 mg/kg) was also administered by oral gavage once a day for 4 weeks. We investigated the number of inflammatory cells, production of T-helper type 2 (Th2) cytokines, chemokine and the total transforming growth factor-β1 (TGF-β1) in bronchoalveolar lavage fluid (BALF); the levels of immunoglobulin E (IgE) in the plasma; the infiltration of inflammatory cells in lung tissue; and the expression of TGF-β1, Smad-3, and collagen in lung tissue. Our results revealed that GGTA lowered the recruitment of inflammatory cells (particularly, lymphocyte); and decreased the production of Th2 cytokines, chemokine and total TGF-β1; and attenuated the levels of total and OVA-specific IgE; and decreased the infiltration of inflammatory cells. Moreover, GGTA significantly reduced the expression of TGF-β1 and Smad-3, and lowered collagen deposition. These results indicate that GGTA reduces airway inflammation and pulmonary fibrosis by regulating Th2 cytokines production and the TGF-β1/Smad-3 pathway, thus providing a potential treatment for chronic asthma. PMID:27741312

  15. Analysis of pulsotypes of salmonella typhi isolates and their clinical profiles in typhoid fever patients

    Directory of Open Access Journals (Sweden)

    Retno K. Soemanto

    2003-03-01

    Full Text Available A study of genotyping (pulsotyping of Salmonella typhi (S. typhi isolates using pulse-field gel electrophoresis (PFGE methods was performed to examine their genetic diversity, and relationship between genetic characteristics and clinical outcomes.  Sixty-six S. typhi isolates obtained from sporadic hospitalized typhoid fever cases were used in this study. Four isolates were found identical and the dendogram constructed showed 33 pulsotypes in which 13 of them can be divided into 30 subtypes. Diversity among them were high as shown by the Dice coefficients that ranged from 0.486 to 1.000. Cluster analysis showed 2 main clusters with 65% degree of similarity, suggested that they were not originated from one clone. Further, at 90% degree of similarity, 9 clusters containing at least 3 isolates were determined to explore any possible existence of relationship between genetic profile and particular clinical outcomes. Clinical manifestations ranged from mild to severe were in fact distributed diversely among these clusters. Although the clinical data obtained were incomplete, 2 out of 4 patients infected by the S. typhi belonged to cluster 1 showed an elevation of total bilirubin, whereas it was not found in 19 other patients distributed in other 8 clusters. Even though specific clinical manifestations were apparently not found to relate with particular clusters of genotypes, S. typhi isolates grouped in cluster 1 seemed to show trophism to hepatobiliary system. (Med J Indones 2003; 12: 13-20 Keywords: S. typhi, typhoid fever, Pulsed-field Gel electrophoresis (PFGE

  16. Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella.

    Science.gov (United States)

    Ramachandran, Girish; Tennant, Sharon M; Boyd, Mary A; Wang, Jin Y; Tulapurkar, Mohan E; Pasetti, Marcela F; Levine, Myron M; Simon, Raphael

    2016-01-01

    Non-typhoidal Salmonella (NTS) serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub-Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera) and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity.

  17. Investigation of a community outbreak of typhoid fever associated with drinking water

    Directory of Open Access Journals (Sweden)

    Kazmi Shahana U

    2009-12-01

    Full Text Available Abstract Background This report is about the investigation of an outbreak of typhoid fever claimed three human lives and left more than 300 people suffered within one week. The aim of this report is to draw the attention of global health community towards the areas that are still far from basic human essentialities. Methods A total of 250 suspected cases of typhoid fever were interviewed, out of which 100 were selected for sample collection on the basis of criteria included temperature > 38°C since the onset of outbreak, abdominal discomfort, diarrhea, vomiting and weakness. Food and water samples were also collected and analyzed microbiologically. Results Inhabitants of village lived in poor and unhygienic conditions with no proper water supply or sewage disposal facilities and other basic necessities of life. They consumed water from a nearby well which was the only available source of drinking water. Epidemiological evidences revealed the gross contamination of well with dead and decaying animal bodies, their fecal material and garbage. Microbiological analysis of household and well water samples revealed the presence of heavy bacterial load with an average total aerobic count 106-109 CFU/ml. A number of Gram positive and Gram negative bacteria including Escherichia coli, Klebsiella, Bacillus species, Staphylococcus species, Enterobacter species, and Pseudomonas aeruginosa were isolated. Lab investigations confirmed the presence of multidrug resistant strain of Salmonella enterica serovar Typhi in 100% well water, 65% household water samples and 2% food items. 22% of clinical stool samples were tested positive with Salmonella enterica serover Typhi Conclusions This study indicated the possible involvement of well water in outbreaks. In order to avoid such outbreaks in future, we contacted the local health authorities and urged them to immediately make arrangements for safe drinking water supply.

  18. Hepatitis A, typhoid and malaria among travelers--surveillance data from Québec (Canada).

    Science.gov (United States)

    Provost, Sylvie; Gagnon, Suzanne; Lonergan, Guy; Bui, Yen-Giang; Labbé, Annie-Claude

    2006-01-01

    Analysis of epidemiological data on health problems related to international travel helps put into perspective preventive interventions for travelers. To document the epidemiological context of travel health interventions in Québec, we reviewed surveillance data for three infectious diseases. The analysis included data collected in the notifiable diseases surveillance system for hepatitis A, typhoid, and malaria cases reported from 2000 to 2002. Additional data were obtained from the provincial hepatitis risk factor database as well as from regional public health departments. More than 40% of cases of hepatitis A for which risk factor information is available are associated with international travel; 20% of these cases were contracted in Mexico and 22% in the West Indies. The risk of acquiring hepatitis A seems to be higher among travelers under 35 years of age; also, given the number of Quebecers traveling to all regions of the world, this risk is proportionally higher in Africa. Data gathered for typhoid indicate that the risk to travelers from Québec is proportionately higher for Quebecers traveling to the Indian subcontinent and whose purpose is to visit family and friends, and for those who stay abroad for 4 weeks or longer. The risk of malaria is greater in Africa (where contracted cases are mostly caused by Plasmodium falciparum). Over half of malaria cases involve individuals traveling abroad for business (including volunteerism), and almost 75% contracted the disease during a stay of a month or more. Nearly half of the cases had not taken chemoprophylaxis. Available data have limitations for infectious disease surveillance among Québec travelers: imprecise number of cases (underdiagnosis and underreporting), imprecise denominators (number of travelers), and lack of data on the characteristics of trips taken. However, despite its limitations, this profile of infectious diseases among travelers from Québec provides interesting data for preventive

  19. Effect of travel distance on household demand for typhoid vaccines: implications for planning.

    Science.gov (United States)

    Kim, Dohyeong; Lauria, Donald T; Poulos, Christine; Dong, Baiqing; Whittington, Dale

    2014-01-01

    Typhoid fever causes millions of illnesses and hundreds of thousands of deaths yearly. Vaccinations would mitigate this problem, but the users would probably have to pay some or most of the cost. Several willingness-to-pay studies have assessed the effect of price on private demand to provide a basis for financial planning of campaigns, but the effect of travel distance, which is a potentially important determinant of demand, has not been studied. This paper thus has two objectives: (i) conduct a willingness-to-pay survey to assess the effects of distance, price and other variables on the private demand for typhoid vaccinations in a rural township of China where a campaign is under consideration; and (ii) embed the demand function in a mathematical model to address three planning questions; should each village have its own clinic, would one clinic be best or should the number of clinics be something in-between? Private vaccine demand was found to depend on and be inelastic with respect to both price and travel distance. A 1-km increase in distance caused the number of vaccinations demanded to decrease the same as a $0.5 increase in price. Thus, the marginal rate of substitution was $0.5 per km. A single clinic would be best for the township only if diseconomies of scale in supplying vaccinations exceeded the marginal rate of substitution. Otherwise, multiple clinics close to users would be optimal. Thus, deciding the number, location and capacities of clinics for vaccination planning is as important as deciding what price(s) to charge.

  20. Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella.

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    Girish Ramachandran

    Full Text Available Non-typhoidal Salmonella (NTS serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub-Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity.

  1. Typhoid fever

    Science.gov (United States)

    ... nih.gov/pubmed/25458731 . Read More Abdominal pain Acute kidney failure Delirium Diarrhea - overview Fatigue Fever Gastrointestinal bleeding Hepatic Malaise Peritonitis Rashes Systemic Weakness Update Date 5/ ...

  2. [Typhoid fever].

    Science.gov (United States)

    Marchou, B

    1996-01-15

    Endemic in regions with poor hygienic conditions, Enteric fevers are imported in France by returning travellers. They are caused by Salmonella strains, mainly S. Typhi, transmitted via fecal-oral route. Salmonella reach the blood stream after proliferating in mesenteric lymph nodes. At an initial stage blood and bone marrow cultures, later on Widal-Felix serology permit diagnosis. Antibiotics have rendered death exceptional. Quinolones and ceftriaxone allow treatments shorter than 10 days. Immunization (Typhim Vi) and improvement of hygienic standards are the cornerstone of prevention.

  3. Identification of immunogenic Salmonella enterica serotype Typhi antigens expressed in chronic biliary carriers of S. Typhi in Kathmandu, Nepal.

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    Richelle C Charles

    Full Text Available BACKGROUND: Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage. METHODOLOGY/PRINCIPAL FINDINGS: To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT, to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479, an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70% chronic carriers, 0 of 8 bile culture-negative controls (0%, 0 of 8 healthy Bangladeshis (0%, and 1 of 8 (12.5% Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present. CONCLUSIONS/SIGNIFICANCE: Further evaluation of YncE and other antigens identified by IVIAT could lead to

  4. [The effect of immunostimulants on the resistance of white mice to the causative agent of typhoid fever].

    Science.gov (United States)

    Sviridov, L P; Stepanov, A V; Konikova, R E; Ustinov, B S

    1990-04-01

    The influence of prodigiosan, salmosan, polyribonate and levamisole on the body nonspecific and specific resistance to S. typhi strain 4446 has been studied. Prodigiosan and salmosan have proved to be the most effective. The injection of these compounds simultaneously with typhoid vaccine (both chemical adsorbed vaccine and alcohol-treated vaccine, enriched with Vi-antigen) significantly increases the survival rate of immunized animals (by 35-45%), elevates the resistance index (1.5- to 2.3-fold) and the effectiveness index of the vaccine (17- to 32-fold) in comparison with the controls. Besides, prodigiosan and salmosan alone are capable of increasing nonspecific resistance to S. typhi strain 4446, which is manifested by an increase of the survival rate of stimulated animals by 61.87%. Proceeding from the results thus obtained, the possibility of good prospects for prodigiosan and salmosan in the prophylaxis of typhoid fever in humans may be inferred. PMID:2385993

  5. CVD 908, CVD 908-htrA, and CVD 909 live oral typhoid vaccines: a logical progression.

    Science.gov (United States)

    Tacket, Carol O; Levine, Myron M

    2007-07-15

    Typhoid fever remains an important public health problem in many parts of the world. Despite the availability of oral Ty21a (Vivotif; Berna Biotech) and parenteral Vi polysaccharide vaccine (Typhim Vi; Aventis Pasteur), improved typhoid fever vaccines have been sought. These include a series of vaccine candidates developed at the Center for Vaccine Development, University of Maryland, based on attenuation of Salmonella enterica serovar Typhi by deletions in the aroC, aroD, and htrA genes. These vaccine candidates, designated "CVD 908," "CVD 908-htrA," and "CVD 909," have been developed and tested in volunteers with variable success. This review summarizes the clinical data that directed the logical progression of this vaccine development strategy.

  6. The association between malaria and non-typhoid Salmonella bacteraemia in children in sub-Saharan Africa: a literature review

    OpenAIRE

    Takem, EN; Roca, A.; Cunnington, A

    2014-01-01

    Plasmodium falciparum malaria and non-typhoid Salmonella (NTS) bacteraemia are both major causes of morbidity and mortality in children in sub-Saharan Africa. Co-infections are expected to occur because of their overlapping geographical distribution, but accumulating evidence indicates that malaria is a risk factor for NTS bacteraemia. A literature review was undertaken to provide an overview of the evidence available for this association, the epidemiology of malaria-NTS co-infection (includi...

  7. Clonal Differences between Non-Typhoidal Salmonella (NTS) Recovered from Children and Animals Living in Close Contact in The Gambia

    OpenAIRE

    Dione, Michel M.; Ikumapayi, Usman N.; Debasish Saha; Mohammed, Nuredin I.; Stanny Geerts; Margareta Ieven; Adegbola, Richard A.; Martin Antonio

    2011-01-01

    BACKGROUND: Non-Typhoidal Salmonella (NTS) is an important cause of invasive bacterial disease and associated with mortality in Africa. However, little is known about the environmental reservoirs and predominant modes of transmission. Our study aimed to study the role of domestic animals in the transmission of NTS to humans in rural area of The Gambia. METHODOLOGY: Human NTS isolates were obtained through an active population-based case-control surveillance study designated to determine the a...

  8. Is travel prophylaxis worth while? Economic appraisal of prophylactic measures against malaria, hepatitis A, and typhoid in travellers.

    OpenAIRE

    Behrens, R. H.; Roberts, J. A.

    1994-01-01

    OBJECTIVES--To estimate the costs and benefits of prophylaxis against travel acquired malaria, typhoid fever, and hepatitis A in United Kingdom residents during 1991. DESIGN--Retrospective analysis of national epidemiological and economic data. MAIN OUTCOME MEASURES--Incidence of travel associated infections in susceptible United Kingdom residents per visit; costs of prophylaxis provision from historical data; benefits to the health sector, community, and individuals in terms of avoided morbi...

  9. Salmonella enterica serovar Typhi O:1,9,12 polysaccharide-protein conjugate as a diagnostic tool for typhoid fever.

    Science.gov (United States)

    Zuñiga, Jessica; Lillo, Luis; Shin, Junghee J; Machavarapu, Rajya L; Quiroga, Teresa; Goycoolea, Manuela; Matsuhiro, Betty; Aron-Hott, L; Godfrey, Henry P; Cabello, Felipe C

    2005-09-01

    Serologic tests play an important role in diagnosis of typhoid fever. In an effort to develop a more defined reagent for these tests, purified Salmonella enterica serovar Typhi (ST) O:1,9,12 polysaccharide was conjugated to human serum albumin (HSA), and the conjugate was purified chromatographically to yield a reagent with 2 moles ST O polysaccharide per mole HSA. In 40 patients with bacteriologically confirmed typhoid fever, significant dot immunobinding titers (> or =20,000) were present in 28 (70%) tested with 100 ng of ST O antigen-HSA (ST O-HSA) conjugate, in 38 (95%) tested with 100 ng of ST lipopolysaccharide, and in 16 (40%) tested with purified unconjugated ST O chains. In sera from 22 patients with other nontyphoid fevers, 2 (9.1%) had such reactivities with 100 ng of ST O-HSA, 1 (4.5%) had such reactivity with 100 ng of ST lipopolysaccharide (4.5%), and none reacted with 100 ng of unconjugated ST O chains. None of the 17 healthy-control sera reacted significantly with any of the ST reagents. None of the patient or control sera reacted with unconjugated HSA. The sensitivity of dot immunobinding for typhoid fever was 70% with 100 ng of ST O-HSA, somewhat lower than that with 100 ng of ST lipopolysaccharide (95%) but similar to that of the Widal H agglutination test with a > or =1/160 cutoff (74%). Specificities of these tests were 91%, 95%, and 86%, respectively. These preliminary results suggest that ST O polysaccharide-protein conjugates could provide a nontoxic, easily quality-controlled synthetic reagent for analysis of human immune responses to ST as well as for the development of new diagnostics and vaccines for typhoid fever.

  10. Feverlike Temperature is a Virulence Regulatory Cue Controlling the Motility and Host Cell Entry of Typhoidal Salmonella

    OpenAIRE

    Elhadad, Dana; McClelland, Michael; Rahav, Galia; Gal-Mor, Ohad

    2014-01-01

    Human infection with typhoidal Salmonella serovars causes a febrile systemic disease, termed enteric fever. Here we establish that in response to a temperature equivalent to fever (39°C–42°C) Salmonella enterica serovars Typhi, Paratyphi A, and Sendai significantly attenuate their motility, epithelial cell invasion, and uptake by macrophages. Under these feverlike conditions, the residual epithelial cell invasion of S. Paratyphi A occurs in a type III secretion system (T3SS) 1–independent man...

  11. Clonal differences between Non-Typhoidal Salmonella (NTS) recovered from children and animals living in close contact in The Gambia

    OpenAIRE

    Dione, M. M.; Ikumapayi, U N; Saha, D.; Mohammed, N. I.; GEERTS, S; Ieven, M; Adegbola, R A; Antonio, M.

    2011-01-01

    BACKGROUND: Non-Typhoidal Salmonella (NTS) is an important cause of invasive bacterial disease and associated with mortality in Africa. However, little is known about the environmental reservoirs and predominant modes of transmission. Our study aimed to study the role of domestic animals in the transmission of NTS to humans in rural area of The Gambia. METHODOLOGY: Human NTS isolates were obtained through an active population-based case-control surveillance study designated to determine the a...

  12. The Influence of Drinking Water Access on the Occurrence of Water-borne Diseases (Diarrhea and Typhoid

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    Khadijah Azhar

    2015-01-01

    Full Text Available Background: Poor and inadequate drinking water supply are the cause of the high occurrence of water-borne diseases,such as diarrhea and typhoid. These diseases often caused an outbreak among the citizens. This article was a furtheranalysis of data obtained from Basic Health Research (Riskesdas in 2007 with the aim to figure out the influence of drinkingwater access against the occurrence of diarrhea and typhoid. Methods: the used samples were taken from all samples ofthe 2007 Riskesdas, which had complete data about drinking water supply. The dependent variables were diarrhea andtyphoid, and the independent variables were total water usage, physical quality of the water, the water access, type offacilities, type of sanitation facilities, hygiene behavior (e. g. hand washing with soap before having and preparing meals,hand washing with soap after defecation, the use of latrine, and characteristic of respondents (educational background,occupation, age, and gender. Analysis was performed by using bivariate and multivariate logistic regression. Results:showed that diarrhea and typhoid were influenced by the difficulty of the access to get water from sources, difficulty levelfor obtaining the water, non physical-standards water, low educational background, behavior of hand washing and latrineusage. Conclusion: was water-borne diseases occured if the access of water was limited, inadequate water’s physicalquality and unhigienic behavior.

  13. Serum bactericidal assay for the evaluation of typhoid vaccine using a semi-automated colony-counting method.

    Science.gov (United States)

    Jang, Mi Seon; Sahastrabuddhe, Sushant; Yun, Cheol-Heui; Han, Seung Hyun; Yang, Jae Seung

    2016-08-01

    Typhoid fever, mainly caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening disease, mostly in developing countries. Enzyme-linked immunosorbent assay (ELISA) is widely used to quantify antibodies against S. Typhi in serum but does not provide information about functional antibody titers. Although the serum bactericidal assay (SBA) using an agar plate is often used to measure functional antibody titers against various bacterial pathogens in clinical specimens, it has rarely been used for typhoid vaccines because it is time-consuming and labor-intensive. In the present study, we established an improved SBA against S. Typhi using a semi-automated colony-counting system with a square agar plate harboring 24 samples. The semi-automated SBA efficiently measured bactericidal titers of sera from individuals immunized with S. Typhi Vi polysaccharide vaccines. The assay specifically responded to S. Typhi Ty2 but not to other irrelevant enteric bacteria including Vibrio cholerae and Shigella flexneri. Baby rabbit complement was more appropriate source for the SBA against S. Typhi than complements from adult rabbit, guinea pig, and human. We also examined the correlation between SBA and ELISA for measuring antibody responses against S. Typhi using pre- and post-vaccination sera from 18 human volunteers. The SBA titer showed a good correlation with anti-Vi IgG quantity in the serum as determined by Spearman correlation coefficient of 0.737 (P typhoid vaccines.

  14. Feverlike Temperature is a Virulence Regulatory Cue Controlling the Motility and Host Cell Entry of Typhoidal Salmonella.

    Science.gov (United States)

    Elhadad, Dana; McClelland, Michael; Rahav, Galia; Gal-Mor, Ohad

    2015-07-01

    Human infection with typhoidal Salmonella serovars causes a febrile systemic disease, termed enteric fever. Here we establish that in response to a temperature equivalent to fever (39 °C-42 °C) Salmonella enterica serovars Typhi, Paratyphi A, and Sendai significantly attenuate their motility, epithelial cell invasion, and uptake by macrophages. Under these feverlike conditions, the residual epithelial cell invasion of S. Paratyphi A occurs in a type III secretion system (T3SS) 1-independent manner and results in restrained disruption of epithelium integrity. The impaired motility and invasion are associated with down-regulation of T3SS-1 genes and class II and III (but not I) of the flagella-chemotaxis regulon. In contrast, we demonstrate up-regulation of particular Salmonella pathogenicity island 2 genes (especially spiC) and increased intraepithelial growth in a T3SS-2-dependent manner. These results indicate that elevated physiological temperature is a novel cue controlling virulence phenotypes in typhoidal serovars, which is likely to play a role in the distinct clinical manifestations elicited by typhoidal and nontyphoidal salmonellae. PMID:25492917

  15. High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children

    LENUS (Irish Health Repository)

    Holt, Kathryn E

    2010-05-31

    Abstract Background Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. Methods We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. Results Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. Conclusions Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.

  16. Chronic Diarrhea

    Science.gov (United States)

    ... infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...

  17. Typhoid fever: hurdles to adequate hand washing for disease prevention among the population of a peri-urban informal settlement in Fiji

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    Mosese Salusalu

    2013-01-01

    Full Text Available Problem/context: The Pacific island nation of Fiji Islands has high rates of endemic typhoid fever which is difficult to diagnose and often underreported. However, the majority of cases are preventable through use of safe water; adequate sanitation; vaccination; and, most sustainable of all, simple hygienic behaviour, such as hand washing with soap (HWWS. Despite many attempts by public health authorities, little progress has been made in the area of environmental adaptation and behaviour change. Action: To explore perceptions of typhoid fever risk among urban squatters and behavioural determinants surrounding HWWS, indigenous Fijians living in informal settlements with high typhoid fever incidence were invited to participate in focus group discussions. In-depth interviews were conducted with community leaders. Outcome: Perceptions of typhoid fever suggest confusion about risk factors, symptoms and communicability. Environmental barriers for hand washing were related to water and soap access. Standard social marketing approaches have been trialled with little clear evidence of impact. Despite this, we continue to advocate for the social and cultural determinants of typhoid prevention to remain central to future public health strategies. Discussion: Despite behaviour change being notoriously difficult, we argue that community-driven behaviour adaptation initiatives based on sound epidemiological evidence and health communication theory are likely to have significant impact and greater likelihood of sustainability.

  18. STUDY ON FEASIBILITY AND LOGISTICS OF VACCINATION WITH TYPHOID VI-VACCINE ON SCHOOL CHILDREN IN NORTH JAKARTA INDONESIA: ANALYSIS OF THE VACCINATION COST

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    Roy G.A. Massie

    2012-11-01

    Full Text Available Background: In recent years, Indonesia government has become increasingly concerned with the issues of financing childhood vaccines and immunization programs including vaccine for typhoid  fever. The objective of the analysis is to provide alternative resources and to provide understandable data generated from the Study on Feasibility and Logistics of Vaccination School Age Children With Typhoid Vi-Vaccine in North Jakarta Indonesia. Methods: The analysis was focus on measurement of the cost for vaccinating school children with Typhoid Vi-vaccine from 18 selected primary schools in North Jakarta. The primary source of data was generated from the actual expenditures that were used in the vaccine delivery program in Indonesia. Results: The Vaccination Cost from the Study on Feasibility and Logistics of Vaccination School Age Children with Typhoid Vi-Vaccine conducted by DOMI project is not applicable for public vaccination program. The program might be feasible to be delivered only in private health sector settings.   Key words: Immunization expenditure, vaccine for typhoid fever, North Jakarta Indonesia

  19. Zebrafish as a novel model for non-typhoidal Salmonella pathogenesis, transmission and vaccine efficacy.

    Science.gov (United States)

    Howlader, Debaki Ranjan; Sinha, Ritam; Nag, Dhrubajyoti; Majumder, Nilanjana; Mukherjee, Priyadarshini; Bhaumik, Ushasi; Maiti, Suhrid; Withey, Jeffrey H; Koley, Hemanta

    2016-09-30

    Salmonella-induced gastroenteritis causes massive morbidity and mortality in both adults and children of developing countries. However, it is difficult to study the mode of infection and vaccine efficacy due to inadequacies of current animal models. For this reason, we have explored using zebrafish as an improved model for non-typhoidal Salmonella (NTS) infection, including Salmonella enterica Typhimurium, Salmonella enterica Enteritidis and Salmonella enterica Weltevreden. In this study, we found that after infection of zebrafish with NTS, severe diarrhea like symptoms were observed and NTS significantly colonized the zebrafish intestine without any manipulation of the normal intestinal microbiota of the fish. Furthermore, these strains can colonize for longer than 72h and induce severe inflammation in the intestine, which may induce fish death. We also found that infected fish can transmit the pathogen into naïve fish. Moreover, we have established that zebrafish is an excellent model for vaccine study. Successive triple bath vaccination with heat-killed single serotype S. Typhimurium and S. Enteritidis immunogen induced protective efficacy against a high dose (10(8)CFU/ml) of infection with these pathogens. This study provides a natural infection model for the study of NTS infection, transmission and vaccine efficacy. PMID:27614779

  20. Hygiene habits and carriers in families with a child who has had typhoid fever

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    M. de la Luz Alvarez

    1992-04-01

    Full Text Available The relationship between asymptomatic shedding of bacterial enteropathogens and the hygiene habits of families who have had a child with typhoid fever (TF are investigated. The sample was made up of 80 families: 40 families in which one child had had TF (Group A and 40 in which no children or either of the parents had had a history of TF (Group B. In each group 20 families belonged to a low socieconomic status (SES and 20 to a high SES. A structured interview was used to evaluate the SES and the hygiene habits of the child; observations were made to measure the hygiene habits of the family (toilet, kitchen and food preparation and bacteriological studies (fecal samples and hand markers. Results show that carriers were more frequent in Group A than in Group B. The bacterial species found were significantly more numerous in Group A than in Group B (fecal samples: E. coli, the classic serotypes, Shigella ssp, and hand markers: E. coli. Families of Group A had higher carriage rates than those of Group B. Finally there exists a significantly higher association between inadequate hygiene habits and carrier families. These results show the need to teach specific habits of proper hygiene to the entire population, because the fact of belonging to the high SES does not in itself preclude inadequate hygiene habits.

  1. Hygiene habits and carriers in families with a child who has had typhoid fever

    Directory of Open Access Journals (Sweden)

    Alvarez M. de la Luz

    1992-01-01

    Full Text Available The relationship between asymptomatic shedding of bacterial enteropathogens and the hygiene habits of families who have had a child with typhoid fever (TF are investigated. The sample was made up of 80 families: 40 families in which one child had had TF (Group A and 40 in which no children or either of the parents had had a history of TF (Group B. In each group 20 families belonged to a low socieconomic status (SES and 20 to a high SES. A structured interview was used to evaluate the SES and the hygiene habits of the child; observations were made to measure the hygiene habits of the family (toilet, kitchen and food preparation and bacteriological studies (fecal samples and hand markers. Results show that carriers were more frequent in Group A than in Group B. The bacterial species found were significantly more numerous in Group A than in Group B (fecal samples: E. coli, the classic serotypes, Shigella ssp, and hand markers: E. coli. Families of Group A had higher carriage rates than those of Group B. Finally there exists a significantly higher association between inadequate hygiene habits and carrier families. These results show the need to teach specific habits of proper hygiene to the entire population, because the fact of belonging to the high SES does not in itself preclude inadequate hygiene habits.

  2. Seroincidence of non-typhoid Salmonella infections: convenience vs. random community-based sampling.

    Science.gov (United States)

    Emborg, H-D; Simonsen, J; Jørgensen, C S; Harritshøj, L H; Krogfelt, K A; Linneberg, A; Mølbak, K

    2016-01-01

    The incidence of reported infections of non-typhoid Salmonella is affected by biases inherent to passive laboratory surveillance, whereas analysis of blood sera may provide a less biased alternative to estimate the force of Salmonella transmission in humans. We developed a mathematical model that enabled a back-calculation of the annual seroincidence of Salmonella based on measurements of specific antibodies. The aim of the present study was to determine the seroincidence in two convenience samples from 2012 (Danish blood donors, n = 500, and pregnant women, n = 637) and a community-based sample of healthy individuals from 2006 to 2007 (n = 1780). The lowest antibody levels were measured in the samples from the community cohort and the highest in pregnant women. The annual Salmonella seroincidences were 319 infections/1000 pregnant women [90% credibility interval (CrI) 210-441], 182/1000 in blood donors (90% CrI 85-298) and 77/1000 in the community cohort (90% CrI 45-114). Although the differences between study populations decreased when accounting for different age distributions the estimates depend on the study population. It is important to be aware of this issue and define a certain population under surveillance in order to obtain consistent results in an application of serological measures for public health purposes.

  3. Multidrug Resistant Salmonella typhi in Asymptomatic Typhoid Carriers among Food Handlers in Namakkal District, Tamil Nadu

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    Senthilkumar B

    2005-01-01

    Full Text Available Purpose: to screen Salmonella typhi in asymptomatic typhoid carriers and to find out drug resistance and ability of the strains to transmit drug resistance to other bacteria. Methods: Cultural characters, biochemical tests, antibiotic sensitivity test (disc diffusion, agarose gel electrophoresis, and conjugation protocols were done. Thirty five stool samples were collected from the suspected food handlers for the study. Results: Among 35 samples, (17.14% yielded a positive result. Out of these 4 (20.0% were women and 2 (13.33% were men. The isolates were tested with a number of conventional antibiotics viz, amikacin, amoxicillin, ampicillin, chloramphenicol, ciprofloxacin, co-trimaxazole, rifampicin, gentamicin, nalidixic acid, ofloxacin and tetracycline. Five isolates were having the multidrug resistant character. Four (66.66% multidrug resistant isolates were found to have plasmids, while one (16.66% multidrug resistant isolate had no plasmid and the chromosome encoded the resistance. Only one strain (16.66% showed single antibiotic resistance in the study and had no plasmid DNA. The molecular weights of the plasmids were determined and found to be 120 kb.The mechanism of spreading of drug resistance through conjugation process was analyzed. In the conjugation studies, the isolates having R+ factor showed the transfer of drug resistance through conjugation, which was determined by the development of antibiotic resistance in the recipients. Conclusion: This study shows that drug resistant strains are able to transfer genes encoding drug resistance.

  4. Comparative study of four time series methods in forecasting typhoid fever incidence in China.

    Directory of Open Access Journals (Sweden)

    Xingyu Zhang

    Full Text Available Accurate incidence forecasting of infectious disease is critical for early prevention and for better government strategic planning. In this paper, we present a comprehensive study of different forecasting methods based on the monthly incidence of typhoid fever. The seasonal autoregressive integrated moving average (SARIMA model and three different models inspired by neural networks, namely, back propagation neural networks (BPNN, radial basis function neural networks (RBFNN, and Elman recurrent neural networks (ERNN were compared. The differences as well as the advantages and disadvantages, among the SARIMA model and the neural networks were summarized and discussed. The data obtained for 2005 to 2009 and for 2010 from the Chinese Center for Disease Control and Prevention were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE, mean absolute percentage error (MAPE, and mean square error (MSE. The results showed that RBFNN obtained the smallest MAE, MAPE and MSE in both the modeling and forecasting processes. The performances of the four models ranked in descending order were: RBFNN, ERNN, BPNN and the SARIMA model.

  5. Preparation and immunogenicity-evaluation of typhoid O-specific polysaccharides bio-conjugate vaccines.

    Science.gov (United States)

    Zhehui, Peng; Chao, Pan; Peng, Sun; Erling, Feng; Jun, Wu; Li, Zhu; Qingzhong, Peng; Hengliang, Wang

    2015-05-01

    Typhoid fever caused by Salmonella Typhi is still a major public health problem in developing countries. In this study, we constructed a genetically modified Salmonella Typhi strain expressing O-specific polysaccharides (OPS) antigen conjugated to a carrier, recombinant Pseudomonas aeruginosa exotoxin A(rEPA N29). The conjugates (OPS-rEPA N29) were further purified and evaluated for their immunogenicity. The results of ELISA showed that the conjugates evoked higher titers of IgG than OPS, suggesting that rEPAN29 increased immunogenicity of OPS significantly as a carrier. Moreover, three injections with 3-week interval evoked slightly higher titers of IgG than three injections with 2-week interval. However, injection of excess conjugates could not evoke higher titers of IgG against lipid polysaccharide (LPS). In summary, our study provides a new strategy for preparing polysaccharides-protein conjugate vaccines as well as similar bio-conjugate vaccines of other Gram-negative pathogens.

  6. Typhoid fever outbreak in Madaya Township, Mandalay Division, Myanmar, September 2000.

    Science.gov (United States)

    Aye, Tin Tin; Siriarayapon, Potjaman

    2004-04-01

    In September 2000, an outbreak of typhoid fever was reported in a rural village of Central Myanmar. The authors investigated the outbreak in the affected village. A suspected case was a person suffering from fever with either constipation, abdominal pain, diarrhoea/bloody diarrhoea. A probable case was a suspected case who had positive result on the diazo urine test or widal test. Based on probable cases, the authors conducted a case-control study comparing history of contact with the cases, water source, and personal hygiene. Control was a person living in the village was not ill and having a negative result for diazo urine test. Among 49 suspected cases, 33 were probable. Attack rate was 1.2%. Three cases had a positive culture for Salmonella typhi and were not drug resistant. The following risk factors were identified: drinking unboiled river water (adjusted OR 12.5, 95%CI 2.8-75.3), history of contact with other patients before the illness (adjusted OR 22, 95%CI 3.5-76.2), no hand washing with soap after defecation (adjusted OR 0.15, 95% CI 0.03-0.81). Environmental investigation result showed that most of the households had unsanitary latrine and some latrines were constructed near the edge of a river. The outbreak subsided quickly after intervention.

  7. Association between the incidence of typhoid and paratyphoid fever and meteorological variables in Guizhou, China

    Institute of Scientific and Technical Information of China (English)

    WANG Lu-xi; LI Xiu-jun; FANG Li-qun; WANG Duo-chun; CAO Wu-chun; KAN Biao

    2012-01-01

    Background Typhoid/paratyphoid fever (TPF) is endemic in Guizhou.We conducted wavelet analysis and Spearman's rank correlation analysis to explore the impact of meteorological variations on TPF infection in Guizhou,in an attempt to assess the risk factors associated with TPF epidemics.Methods We examined the association between TPF incidence in Guizhou and temperature,precipitation and relative humidity using 24 years of data from 1984 to 2007.Periodicities of TPF incidence and the impact of climate factors on the TPF were detected by Spearman's rank correlation and wavelet analysis,Results Temperature and precipitation with a 1-month lag were positively correlated with the monthly incidence of TPF.The multiyear incidence pattern of TPF in Guizhou was explicitly periodic.Moreover,the association and driving effect of precipitation on TPF were observed,and the results showed that the incidence of TPF in Guizhou had a closer correlation with precipitation than with temperature.Conclusions Safe water supply is the key issue for TPF control in Guizhou.Moreover,climate variation might impact the enteric infections,which may inform policy assessment for TPF control in Guizhou.

  8. Curcumin increases the pathogenicity of Salmonella enterica serovar Typhimurium in murine model.

    Directory of Open Access Journals (Sweden)

    Sandhya A Marathe

    Full Text Available Curcumin has gained immense importance for its vast therapeutic and prophylactic applications. Contrary to this, our study reveals that it regulates the defense pathways of Salmonella enterica serovar Typhimurium (S. Typhimurium to enhance its pathogenicity. In a murine model of typhoid fever, we observed higher bacterial load in Peyer's patches, mesenteric lymph node, spleen and liver, when infected with curcumin-treated Salmonella. Curcumin increased the resistance of S. Typhimurium against antimicrobial agents like antimicrobial peptides, reactive oxygen and nitrogen species. This increased tolerance might be attributed to the up-regulation of genes involved in resistance against antimicrobial peptides--pmrD and pmrHFIJKLM and genes with antioxidant function--mntH, sodA and sitA. We implicate that iron chelation property of curcumin have a role in regulating mntH and sitA. Interestingly, we see that the curcumin-mediated modulation of pmr genes is through the PhoPQ regulatory system. Curcumin downregulates SPI1 genes, required for entry into epithelial cells and upregulates SPI2 genes required to intracellular survival. Since it is known that the SPI1 and SPI2 system can be regulated by the PhoPQ system, this common regulator could explain curcumin's mode of action. This data urges us to rethink the indiscriminate use of curcumin especially during Salmonella outbreaks.

  9. Treatment failure in a typhoid patient infected with nalidixic acid resistant S. enterica serovar Typhi with reduced susceptibility to Ciprofloxacin: a case report from Cameroon

    Directory of Open Access Journals (Sweden)

    Asonganyi Etienne DN

    2005-06-01

    Full Text Available Abstract Background Fluoroquinolones or third generation cephalosporins are the drugs of choice for the treatment of typhoid fever. Treatment failure with fluoroquinolones has been reported in Asia and Europe. We report a case of ciprofloxacin treatment failure in typhoid fever in Cameroon. Case presentation A 29-year-old female patient with suspected typhoid fever from Kumba, Cameroon, yielded growth of Salmonella enterica serovar Typhi in blood culture. The isolate was resistant to nalidixic acid but sensitive to ciprofloxacin by disc diffusion test. However, the patient did not respond to treatment with ciprofloxacin, although the isolate was apparently susceptible to ciprofloxacin. Conclusion Treatment failure with ciprofloxacin in our case indicates the presence of nalidixic acid resistant S. enterica serovar Typhi (NARST with reduced susceptibility to ciprofloxacin in Cameroon (Central Africa.

  10. Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni

    Science.gov (United States)

    Pereira, Thiago Almeida; Syn, Wing-Kin; Amâncio, Frederico Figueiredo; Cunha, Pedro Henrique Diniz; Caporali, Julia Fonseca Morais; Trindade, Guilherme Vaz de Melo; Santos, Elisângela Trindade; Souza, Márcia Maria; Andrade, Zilton Araújo; Witek, Rafal P; Secor, William Evan; Pereira, Fausto Edmundo Lima; Lambertucci, José Roberto; Diehl, Anna Mae

    2016-01-01

    Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and

  11. Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from patients having acute diarrhoeal disease

    International Nuclear Information System (INIS)

    Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearence of multiple drung resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhodial Salmonella isolated from faecal samples of patients with acute diarroheal disease attending the outpatient and inpatient department of a hospital in Saudi Arabia during the years 1999 to 2002. Non-typhodial Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacinwere determined by the agar dilution method. During the study period , 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulphamethoxazole in 18.5%of the strains. Nalidixic acid resistance was encounterd in 9.9% and ciprofloxacin esistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.51% in 2002 ( p=0.0007)and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002( p=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal salmonella isolated during 2002. The MIC was >256 ug /ml to nalidixic acid and 8 to 16 ug/ml to ciprofloxacin. The increasing rate of antimicrobial resistance encountered among non-tyophoidal Salmonella necessiate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increasein resistance and should should be restricted. (author)

  12. Serum bactericidal assay for the evaluation of typhoid vaccine using a semi-automated colony-counting method.

    Science.gov (United States)

    Jang, Mi Seon; Sahastrabuddhe, Sushant; Yun, Cheol-Heui; Han, Seung Hyun; Yang, Jae Seung

    2016-08-01

    Typhoid fever, mainly caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening disease, mostly in developing countries. Enzyme-linked immunosorbent assay (ELISA) is widely used to quantify antibodies against S. Typhi in serum but does not provide information about functional antibody titers. Although the serum bactericidal assay (SBA) using an agar plate is often used to measure functional antibody titers against various bacterial pathogens in clinical specimens, it has rarely been used for typhoid vaccines because it is time-consuming and labor-intensive. In the present study, we established an improved SBA against S. Typhi using a semi-automated colony-counting system with a square agar plate harboring 24 samples. The semi-automated SBA efficiently measured bactericidal titers of sera from individuals immunized with S. Typhi Vi polysaccharide vaccines. The assay specifically responded to S. Typhi Ty2 but not to other irrelevant enteric bacteria including Vibrio cholerae and Shigella flexneri. Baby rabbit complement was more appropriate source for the SBA against S. Typhi than complements from adult rabbit, guinea pig, and human. We also examined the correlation between SBA and ELISA for measuring antibody responses against S. Typhi using pre- and post-vaccination sera from 18 human volunteers. The SBA titer showed a good correlation with anti-Vi IgG quantity in the serum as determined by Spearman correlation coefficient of 0.737 (P < 0.001). Taken together, the semi-automated SBA might be efficient, accurate, sensitive, and specific enough to measure functional antibody titers against S. Typhi in sera from human subjects immunized with typhoid vaccines. PMID:27216239

  13. Identification of murine complement receptor type 2.

    OpenAIRE

    Fingeroth, J D; Benedict, M A; Levy, D.N.; Strominger, J L

    1989-01-01

    A rabbit antiserum reactive with the human complement component C3d/Epstein-Barr virus receptor (complement receptor type 2, CR2) immunoprecipitates a Mr 155,000 murine B-cell surface antigen. The apparent molecular weight and cellular distribution of this murine antigen are similar to those of human CR2. Cells expressing the murine protein bind sheep erythrocytes coated with antibody and murine C1-C3d but do not bind Epstein-Barr virus at all. The monospecific antiserum to human CR2 together...

  14. Synergistic effect of mutations in invA and lpfC on the ability of Salmonella typhimurium to cause murine typhoid.

    Science.gov (United States)

    Bäumler, A J; Tsolis, R M; Valentine, P J; Ficht, T A; Heffron, F

    1997-06-01

    Penetration of the intestinal mucosa at areas of Peyer's patches is an important first step for Salmonella typhimurium to produce lethal systemic disease in mice. However, mutations in genes that are important for intestinal invasion result in only moderately decreased virulence of S. typhimurium for mice. Here we report that combining mutations in invA and lpfC, two genes necessary for entry into Peyer's patches, results in a much stronger attenuation of S. typhimurium than inactivation of either of these genes alone. An S. typhimurium invA lpfC mutant was 150-fold attenuated by the oral route of infection but was fully virulent when the intestine was bypassed by intraperitoneal challenge of mice. During mixed-infection experiments, the S. typhimurium invA lpfC mutant showed a strong defect in colonizing Peyer's patches and mesenteric lymph nodes. These data suggest that mutations in invA and lpfC deactivate distinct pathways for intestinal penetration and colonization of Peyer's patches. While the inv-mediated pathway is widely distributed, the lpf operon is absent from many phylogenetic groups within the genus Salmonella. To investigate how acquisition of the lpf-mediated pathway for mucosal penetration contributed to evolution of virulence, we studied the relationship between the presence of the lpf operon and the pathogenicity for mice of 18 isolates representing 14 Salmonella serotypes. Only strains possessing the lpf operon were able to cause lethal infection in mice. These data show that both the invA- and lpfC-mediated pathways of intestinal perforation are conserved in mouse virulent Salmonella serotypes.

  15. Eradication of Salmonella Typhimurium infection in a murine model of typhoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin

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    Karki Tõnis

    2008-08-01

    Full Text Available Abstract Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the ileum mucosa. The selected bacteriological, histological and biochemical methods were applied. Results Combined treatment with L. fermentum ME-3 and ofloxacin eradicated Salmonella Typhimurium from blood, ileum and liver, decreased the number of animals with liver and spleen granulomas and reduced the value of lipid peroxides in the ileum mucosa. Higher total counts of intestinal lactobacilli in all experimental groups were associated with the absence of liver granulomas. Conclusion The antimicrobial and antioxidative probiotic L. fermentum ME-3 combined with ofloxacin enhances the eradication of experimental S. Typhimurium infection. These observations on probiotic and antimicrobial co-action may serve as basis to develop new strategies for treatment of invasive bacterial infections of the gut.

  16. Notes from the Field: Typhoid Fever Outbreak Associated with an Asymptomatic Carrier at a Restaurant - Weld County, Colorado, 2015.

    Science.gov (United States)

    Hancock-Allen, Jessica; Cronquist, Alicia B; Peden, JoRene; Adamson, Debra; Corral, Nereida; Brown, Kerri

    2016-01-01

    On September 11, 2015, a single case of typhoid fever, caused by Salmonella Typhi infection, was reported to the Colorado Department of Public Health and Environment (CDPHE). Because the patient (patient A) had symptom onset September 2 and had traveled internationally for 4 days 60 days before symptom onset, the case initially was thought to be travel-associated* (1,2). On October 1, a second case of S. Typhi infection was reported in patient B, with symptom onset September 20. Patient B reported no international travel or contact with ill persons or known carriers. Patients A and B resided approximately 6 miles (10 kilometers) apart and had no discernible epidemiologic connection. Family members of patients A and B tested negative for S. Typhi. CDPHE and the Weld County Department of Public Health and Environment (WCDPHE) investigated to 1) determine whether these cases represented a larger outbreak, 2) identify common exposure sources, and 3) stop transmission. Investigators determined that the typhoid fever in both patients and in a third patient (patient C) was associated with eating in the same restaurant during a 5-day period. PMID:27310090

  17. Emergence and serovar profiling of non-typhoidal Salmonellae (NTS) isolated from gastroenteritis cases-A study from South India.

    Science.gov (United States)

    Ballal, Mamatha; Devadas, Suganthi Martena; Shetty, Vignesh; Bangera, Sohan Rodney; Ramamurthy, Thandavarayan; Sarkar, Anirban

    2016-01-01

    Human infection with non-typhoidal Salmonella (NTS) serovars is often a neglected and undiagnosed infection in the developing world. Invasive NTS is now being established as having a new and emerging pathogenic role. There is not sufficient data on the prevalence of NTS serovars and their antibiotic susceptibility pattern from India. Faecal specimens collected from patients with acute gastroenteritis were processed to isolate Salmonella according to the standard protocol for a period from January 2011-December 2014. Salmonella isolates were serotyped and tested for antibiotic susceptibility. Of the total 320 (10.04%) bacterial enteric pathogens isolated, 64 (20%) were non-typhoidal Salmonella. Among the serogroup, O:4 (B) (n = 26; 40.6%) was found to be the commonest followed by O:7 (C1) (n = 11; 17.1%) and O:3,10 (E1) (n = 11; 17.1%). NTS infection in cancer patients could also be termed as nosocomial NTS diarrhoea due to primary community infection with prolonged incubation periods, consumption of contaminated food during hospital stay or Nosocomially acquired infection. Serovar Oslo has been predominant (9/17) in NTS isolates from cancer patients, whereas serovars Bovismorbificans, Wangata and Schleissheim have been reported for the first time in the country. The isolates were mostly susceptible to antibiotics except Salmonella ser Kentucky, which showed resistance to ciprofloxacin is reported for the first time in the country. Continuous surveillance is required to monitor resistance of NTS isolates. PMID:27300440

  18. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals.

    Science.gov (United States)

    Szu, S C; Stone, A L; Robbins, J D; Schneerson, R; Robbins, J B

    1987-11-01

    The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions.

  19. Efficacy of a locally produced, Chinese Vi polysaccharide typhoid fever vaccine during six years of follow-up.

    Science.gov (United States)

    Acosta, Camilo J; Hong-Hui, Yang; Ning, Wang; Qion, Gao; Qun, Deng; Xiaolei, Ma; Baode, Zhou; Liu, Wei; Danovaro-Holliday, M Carolina; Ochiai, R Leon; Wang, Xuan-Yi; Kim, Deok-Ryun; Zhi-Yi, Xu; Bai-Qing, Dong; Galindo, Claudia M; Clemens, John D

    2005-12-01

    A locally produced Vi polysaccharide vaccine against typhoid fever was licensed in China following two placebo-controlled, efficacy trials conducted in the early 1990s in Baoying, Jiangsu Province, and Quan-zhou, Guangxi Province. The two trials each enrolled over 80,000 participants and followed participants for 12 and 19 months post-vaccination, respectively. To define the long-term efficacy of this vaccine, we retrospectively assessed the occurrence of typhoid fever, diagnosed with clinical and serological criteria, in the two study populations for 6 years following vaccination. During the second year following vaccination, vaccine efficacy was 100% (95% CI: 17%, 100%) in Baoying and 85% (95% CI: 49%, 96%) in Quan-zhou. There was suggestive protection (51%; PE: -95%, 88%) during the third year in Baoying, nearly identical to the level observed in the third year of an earlier trial in South Africa. These results confirm that this vaccine protects for at least 2 years, and are consistent with the assertion that the vaccine protects for at least 3 years.

  20. Arthur Conan Doyle (1859-1930): Physician during the typhoid epidemic in the Anglo-Boer War (1899-1902).

    Science.gov (United States)

    Cirillo, Vincent J

    2014-02-01

    When the Anglo-Boer War broke out in October 1899, Arthur Conan Doyle, a retired ophthalmologist, was already famous as the creator of Sherlock Holmes. Motivated by patriotism and adventure, Doyle joined the medical staff of a private field hospital endowed by philanthropist John Langman (1846-1928). Langman Hospital opened in Bloemfontein, South Africa, at the height of that city's typhoid fever epidemic which raged from April to June 1900. There were nearly 5000 cases of typhoid and 1000 deaths but official statistics do not truly reflect the magnitude of the suffering. Doyle argued that the British Army had made a major mistake by not making antityphoid inoculation compulsory. Because of the new vaccine's side effects, 95% of the soldiers refused immunization. Despite his strong opinions, Doyle failed to press the issue of compulsory inoculation when he testified before two Royal Commissions investigating the medical and military management of the war in South Africa. One can only imagine how the army might have benefited from the new idea of prophylactic vaccination in preventive medicine if Doyle had not let these opportunities slip away. As a consequence, antityphoid inoculation was still voluntary when Great Britain entered World War I in August 1914.

  1. Arthur Conan Doyle (1859-1930): Physician during the typhoid epidemic in the Anglo-Boer War (1899-1902).

    Science.gov (United States)

    Cirillo, Vincent J

    2014-02-01

    When the Anglo-Boer War broke out in October 1899, Arthur Conan Doyle, a retired ophthalmologist, was already famous as the creator of Sherlock Holmes. Motivated by patriotism and adventure, Doyle joined the medical staff of a private field hospital endowed by philanthropist John Langman (1846-1928). Langman Hospital opened in Bloemfontein, South Africa, at the height of that city's typhoid fever epidemic which raged from April to June 1900. There were nearly 5000 cases of typhoid and 1000 deaths but official statistics do not truly reflect the magnitude of the suffering. Doyle argued that the British Army had made a major mistake by not making antityphoid inoculation compulsory. Because of the new vaccine's side effects, 95% of the soldiers refused immunization. Despite his strong opinions, Doyle failed to press the issue of compulsory inoculation when he testified before two Royal Commissions investigating the medical and military management of the war in South Africa. One can only imagine how the army might have benefited from the new idea of prophylactic vaccination in preventive medicine if Doyle had not let these opportunities slip away. As a consequence, antityphoid inoculation was still voluntary when Great Britain entered World War I in August 1914. PMID:24585840

  2. Emergence and serovar profiling of non-typhoidal Salmonellae (NTS) isolated from gastroenteritis cases-A study from South India.

    Science.gov (United States)

    Ballal, Mamatha; Devadas, Suganthi Martena; Shetty, Vignesh; Bangera, Sohan Rodney; Ramamurthy, Thandavarayan; Sarkar, Anirban

    2016-01-01

    Human infection with non-typhoidal Salmonella (NTS) serovars is often a neglected and undiagnosed infection in the developing world. Invasive NTS is now being established as having a new and emerging pathogenic role. There is not sufficient data on the prevalence of NTS serovars and their antibiotic susceptibility pattern from India. Faecal specimens collected from patients with acute gastroenteritis were processed to isolate Salmonella according to the standard protocol for a period from January 2011-December 2014. Salmonella isolates were serotyped and tested for antibiotic susceptibility. Of the total 320 (10.04%) bacterial enteric pathogens isolated, 64 (20%) were non-typhoidal Salmonella. Among the serogroup, O:4 (B) (n = 26; 40.6%) was found to be the commonest followed by O:7 (C1) (n = 11; 17.1%) and O:3,10 (E1) (n = 11; 17.1%). NTS infection in cancer patients could also be termed as nosocomial NTS diarrhoea due to primary community infection with prolonged incubation periods, consumption of contaminated food during hospital stay or Nosocomially acquired infection. Serovar Oslo has been predominant (9/17) in NTS isolates from cancer patients, whereas serovars Bovismorbificans, Wangata and Schleissheim have been reported for the first time in the country. The isolates were mostly susceptible to antibiotics except Salmonella ser Kentucky, which showed resistance to ciprofloxacin is reported for the first time in the country. Continuous surveillance is required to monitor resistance of NTS isolates.

  3. Murine Typhus and Febrile Illness, Nepal

    OpenAIRE

    Zimmerman, Mark D.; Murdoch, David R.; Rozmajzl, Patrick J.; Basnyat, Buddha; Woods, Christopher W.; Richards, Allen L.; Belbase, Ram Hari; Hammer, David A.; Anderson, Trevor P.; Reller, L. Barth

    2008-01-01

    Murine typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell during the winter. No characteristics clearly distinguished typhus patients from those with blood culture–positive enteric fever.

  4. Epidemiologic characteristics of typhoid and paratyphoid fever of related drug resistance and molecular types regarding Salmonella typhi and S. paratyphi,in Jiangsu province

    Institute of Scientific and Technical Information of China (English)

    庄菱

    2013-01-01

    Objective To explore the distribution of prevalence rates of typhoid and paratyphoid,with drug resistance and molecular types of Salmonella(S.) typhi and S. paratyphi in Jiangsu province. Methods Data,collected by the national infectious disease reporting system in Jiangsu province from 2007 to 2011,was analyzed. K-B method was

  5. Formative research and development of an evidence-based communication strategy: the introduction of Vi typhoid fever vaccine among school-aged children in Karachi, Pakistan.

    Science.gov (United States)

    Pach, Alfred; Tabbusam, Ghurnata; Khan, M Imran; Suhag, Zamir; Hussain, Imtiaz; Hussain, Ejaz; Mumtaz, Uzma; Haq, Inam Ul; Tahir, Rehman; Mirani, Amjad; Yousafzai, Aisha; Sahastrabuddhe, Sushant; Ochiai, R Leon; Soofi, Sajid; Clemens, John D; Favorov, Michael O; Bhutta, Zulfiqar A

    2013-01-01

    The authors conducted formative research (a) to identify stakeholders' concerns related to typhoid fever and the need for disease information and (b) to develop a communication strategy to inform stakeholders and address their concerns and motivate for support of a school-based vaccination program in Pakistan. Data were collected during interactive and semi-structured focus group discussions and interviews, followed by a qualitative analysis and multidisciplinary consultative process to identify an effective social mobilization strategy comprised of relevant media channels and messages. The authors conducted 14 focus group discussions with the parents of school-aged children and their teachers, and 13 individual interviews with school, religious, and political leaders. Parents thought that typhoid fever was a dangerous disease, but were unsure of their children's risk. They were interested in vaccination and were comfortable with a school-based vaccination if conducted under the supervision of trained and qualified staff. Teachers and leaders needed information on typhoid fever, the vaccine, procedures, and sponsors of the vaccination program. Meetings were considered the best form of information dissemination, followed by printed materials and mass media. This study shows how qualitative research findings can be translated into an effective social mobilization and communication approach. The findings of the research indicated the importance of increasing awareness of typhoid fever and the benefits of vaccination against the disease. Identification and dissemination of relevant, community-based disease and vaccination information will increase demand and use of vaccination.

  6. The feasibility of a school-based VI polysaccharide vaccine mass immunization campaign in Hue City, central Vietnam: streamlining a typhoid fever preventive strategy.

    Science.gov (United States)

    Thiem, Vu Dinh; Danovaro-Holliday, M Carolina; Canh, Do Gia; Son, Nguyen Dinh; Hoa, Nyugen Thai; Thuy, Dang Thi Dieu; Ochiai, R Leon; Lan, Nguyen Thi; Hop, Tran Quang; Ali, Mohammad; Park, Jin Kyung; Abu-Elyazeed, Remon; Holliday, Kris; Ivanoff, Bernard; Anh, Dang Duc; Pang, Tikki; Donner, Allan; Galindo, Claudia M; Trach, Dang Duc; Clemens, John D; Acosta, Camilo J

    2006-05-01

    We report the coverage, safety, and logistics of a school-based typhoid fever immunization campaign that took place in Hue City, central Vietnam; a typhoid fever endemic area. A cluster-randomized evaluation-blinded controlled trial was designed where 68 schools (cluster) were randomly allocated the single dose Vi polysaccharide vaccine (Typherix) or the active control hepatitis A vaccine (Havrix). A safety surveillance system was implemented. A total of 32,267 children were immunized with a coverage of 57.5%. Strong predictors for vaccination were attending primary schools, peri-urban location of the school, and low family income. Human resources were mainly schoolteachers and the campaign was completed in about 1 month. Most adverse events reported were mild. Safe injection and safe sharp-waste disposal practices were followed. A typhoid fever school-based immunization campaign was safe and logistically possible. Coverage was moderate and can be interpreted as the minimum that could have been achievable because individual written informed consent procedures were sought for the first time in Hue City and the trial nature of the campaign. The lessons learned, together with cost-effectiveness results to be obtained by the end of follow-up period, will hopefully accelerate the introduction of Vi typhoid fever vaccine in Vietnam.

  7. Formative research and development of an evidence-based communication strategy: the introduction of Vi typhoid fever vaccine among school-aged children in Karachi, Pakistan.

    Science.gov (United States)

    Pach, Alfred; Tabbusam, Ghurnata; Khan, M Imran; Suhag, Zamir; Hussain, Imtiaz; Hussain, Ejaz; Mumtaz, Uzma; Haq, Inam Ul; Tahir, Rehman; Mirani, Amjad; Yousafzai, Aisha; Sahastrabuddhe, Sushant; Ochiai, R Leon; Soofi, Sajid; Clemens, John D; Favorov, Michael O; Bhutta, Zulfiqar A

    2013-01-01

    The authors conducted formative research (a) to identify stakeholders' concerns related to typhoid fever and the need for disease information and (b) to develop a communication strategy to inform stakeholders and address their concerns and motivate for support of a school-based vaccination program in Pakistan. Data were collected during interactive and semi-structured focus group discussions and interviews, followed by a qualitative analysis and multidisciplinary consultative process to identify an effective social mobilization strategy comprised of relevant media channels and messages. The authors conducted 14 focus group discussions with the parents of school-aged children and their teachers, and 13 individual interviews with school, religious, and political leaders. Parents thought that typhoid fever was a dangerous disease, but were unsure of their children's risk. They were interested in vaccination and were comfortable with a school-based vaccination if conducted under the supervision of trained and qualified staff. Teachers and leaders needed information on typhoid fever, the vaccine, procedures, and sponsors of the vaccination program. Meetings were considered the best form of information dissemination, followed by printed materials and mass media. This study shows how qualitative research findings can be translated into an effective social mobilization and communication approach. The findings of the research indicated the importance of increasing awareness of typhoid fever and the benefits of vaccination against the disease. Identification and dissemination of relevant, community-based disease and vaccination information will increase demand and use of vaccination. PMID:23330632

  8. Genomic characterisation of invasive non-typhoidal Salmonella enterica Subspecies enterica Serovar Bovismorbificans isolates from Malawi.

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    Christina Bronowski

    2013-11-01

    Full Text Available BACKGROUND: Invasive Non-typhoidal Salmonella (iNTS are an important cause of bacteraemia in children and HIV-infected adults in sub-Saharan Africa. Previous research has shown that iNTS strains exhibit a pattern of gene loss that resembles that of host adapted serovars such as Salmonella Typhi and Paratyphi A. Salmonella enterica serovar Bovismorbificans was a common serovar in Malawi between 1997 and 2004. METHODOLOGY: We sequenced the genomes of 14 Malawian bacteraemia and four veterinary isolates from the UK, to identify genomic variations and signs of host adaptation in the Malawian strains. PRINCIPAL FINDINGS: Whole genome phylogeny of invasive and veterinary S. Bovismorbificans isolates showed that the isolates are highly related, belonging to the most common international S. Bovismorbificans Sequence Type, ST142, in contrast to the findings for S. Typhimurium, where a distinct Sequence Type, ST313, is associated with invasive disease in sub-Saharan Africa. Although genome degradation through pseudogene formation was observed in ST142 isolates, there were no clear overlaps with the patterns of gene loss seen in iNTS ST313 isolates previously described from Malawi, and no clear distinction between S. Bovismorbificans isolates from Malawi and the UK. The only defining differences between S. Bovismorbificans bacteraemia and veterinary isolates were prophage-related regions and the carriage of a S. Bovismorbificans virulence plasmid (pVIRBov. CONCLUSIONS: iNTS S. Bovismorbificans isolates, unlike iNTS S. Typhiumrium isolates, are only distinguished from those circulating elsewhere by differences in the mobile genome. It is likely that these strains have entered a susceptible population and are able to take advantage of this niche. There are tentative signs of convergent evolution to a more human adapted iNTS variant. Considering its importance in causing disease in this region, S. Bovismorbificans may be at the beginning of this process

  9. Non-typhoidal Salmonella bacteraemia: Epidemiology, clinical characteristics and its' association with severe immunosuppression

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    Fatt Quek

    2009-05-01

    Full Text Available Abstract Background Non-typhoidal Salmonella (NTS is increasingly recognized as an important pathogen associated with bacteraemia especially in immunosuppressed patients. However, there is limited data specifically describing the clinical characteristics and outcome amongst the immunosuppressed patients. Methods A total of 56,707 blood culture samples and 5,450 stool samples were received by the microbiology laboratory at a tertiary referral hospital in Malaysia, during a 4-year study period. Out of these samples, 55 non-duplicate NTS isolates were identified from blood and 121 from stool. A retrospective analysis of the 55 patients with NTS bacteraemia was then conducted to determine the predominant NTS serovars causing bacteraemia and its' blood invasive potential, epidemiological data, clinical characteristics and antimicrobial susceptibility. Patients were then grouped as immunosuppressed and non-immunosuppressed to determine the association of severe immunosuppression on clinical features. Data was analyzed using the Statistical Package for Social Sciences (SPSS version 15.0 using the non-parametric Mann-Whitney test, Fisher's exact test or Chi-squared test. The odds ratio (OR and its 95% confidence intervals (CI were calculated. The P-value Results Out of 55 NTS bacteraemia cases identified, 81.8% (45/55 were community-acquired. Salmonella enterica serovar Enteritidis had the highest blood invasiveness. An extra-intestinal focus of infection was noted in 30.9% (17/55 of the patients, most commonly involving the lungs and soft tissue. 90.9% (50/55 of the patients had an underlying disease and 65.5% (36/55 of the patients had severe clinical immunosuppressive condition with malignancy and HIV being the most common. Immunosuppressed patients had higher mortality (P = 0.04, presented more commonly with primary bacteraemia (P = 0.023, leukopenia (P = 0.001 and opportunistic infections (P = 0.01. In contrast, atherosclerotic conditions (P = 0

  10. 伤寒的现状分析及预防控制%Analysis on current situation and strategies of prevention and control for typhoid fever

    Institute of Scientific and Technical Information of China (English)

    何莓; 王惟信; 华羚; 张宏; 许震生

    2012-01-01

    伤寒是由伤寒杆菌引起的严重急性传染病,主要发生在亚洲、非洲和拉丁美洲地区,严重威胁人类健康.伤寒杆菌经粪一口途径传播,人类是唯一的传染源,因此伤寒与环境和食品卫生状况密切相关.近年来多重耐药菌株的出现,使伤寒的抗生素治疗日益复杂,因此严格遵守饮食和饮水卫生及接种伤寒疫苗仍是预防控制该病的主要手段.本文就伤寒的疾病特征、流行分布、多重耐药情况、预防控制及疫苗应用等情况进行了综述.%Typhoid fever is an acute, life-threatening infectious illness caused by salmonella typhosa, which occurs mainly in Asia, Africa and Latin America. Transmission of typhoid fever occurs via the fecal-oral route. Humans are the only source. Personal hygiene and appropriate sanitation are thought to be closely related to typhoid infection. In recent years, the emergence of multidrug resistance in S. typhi has complicated the treatment, food and water precautions and vaccination against typhoid fever remain the essential preventive strategies. The article reviews the feature of typhoid fever, epidemic distribution, multidrug resistance, prevention and control and vaccine application, etc.

  11. Establishment of a Murine Model of Chronic Graft-Versus-Host Disease After Minor Histocompatibility Antigen Mismatched Bone Marrow Transplantation%miHA不合异基因骨髓移植后慢性移植物抗宿主病小鼠模型的建立

    Institute of Scientific and Technical Information of China (English)

    黄欣; 翁建宇; 吴萍; 童嘉琦; 杜欣

    2014-01-01

    Objective To establish a murine model of chronic graft-versus-host disease (cGVHD) after major histocompatibility complex (MHC) matched and minor histocompatibility antigen (miHA) mismatched allogeneic bone marrow transplantation,and to provide in vivo research tools for cGVHD.Methods 20 recipients BALB/c (H2d) female mice were included in this study.They were divided into blank control group (n =5),irradiation control group (n =5),transplantation group (n =5) and the cGVHD group (n=5).In addition to the blank control group,the rest of the three groups of mice were irradiated with 700 cGy dose of linear accelerator.Then the irradiation control group were injected with 0.2 ml PPMI 1640; the trarsplantation group were injected with 8 × 106 bone-marrow cells,and cGVHD group were injected with bone-marrow cells and spleen cells (8× 106,1 ∶ 1) from B10.D2(Hc1 H2d H2-T18c) male mice.The observed items post-transplantation included hematopoietic reconstruction,implant,and general condition.Clinical scores were assessed every 3 days after +14 d.At + 50 d,mice were put to death for evaluation target organ pathological changes.Animal Intervention met animal ethical standard.Results Mice in transplantation groups were in hematopoietic reconstruction at +7 d,and all survived to the end point (+ 50 d).Chromosomes of recipient mice were in donor form.Clinical scores of cGVHD group have been more than 0.6 since +20 d.Pathological changes of skin,liver and lung were obviously,and pathological scores were significant higher than those of transplantation control groups (F=88.02,P< 0.05).Conclusions Irradiation dose for 700 cGy,8× 106 of bone marrow and spleen cell number infusion induce a successful cGVHD murine model,which might be an ideal study model of clinical cGVHD after bone marrow transplantation.%目的 通过主要组织相容性复合物(MHC)相合,次要组织相容性抗原(miHA)不合的异基因骨髓移植,建立慢性移植物抗宿主病(cGVHD)小鼠模型,

  12. Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study.

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    Teresa Fiebig

    Full Text Available Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.

  13. Antibody responses against xenotropic murine leukemia virus-related virus envelope in a murine model.

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    Natalia Makarova

    Full Text Available BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC. Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP that had the size and morphology of live infectious XMRV. RESULTS: Immunization elicited Env-specific binding and neutralizing antibodies (NAb against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations. CONCLUSIONS: Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.

  14. A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

    OpenAIRE

    Yang Hong-hui; Liang Gui-chen; Ivanoff Bernard; Ali Mohammad; Park Jin-Kyung; Gong Jian; Tang Zhen-zhu; Tan Dong-mei; Wang Ming-liu; Liao He-zhuang; Zhou Bao-de; Zhang Jie; Danovaro-Holliday M Carolina; Page Anne-Laure; Ochiai R Leon

    2005-01-01

    Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated t...

  15. Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis.

    Science.gov (United States)

    Mata-Santos, T; Mata-Santos, H A; Carneiro, P F; De Moura, K C G; Fenalti, J M; Klafke, G B; Cruz, L A X; Martins, L H R; Pinto, N F; Pinto, M C F R; Berne, M E A; Da Silva, P E A; Scaini, C J

    2016-04-01

    Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug. PMID:26887285

  16. Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses.

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    Emiley A Eloe-Fadrosh

    Full Text Available The resident microbial consortia of the human gastrointestinal tract play an integral role in modulating immune responses both locally and systemically. However, detailed information regarding the effector immune responses after vaccine administration in relation to the gastrointestinal microbiota is absent. In this study, the licensed oral live-attenuated typhoid vaccine Ty21a was administered in a clinical study to investigate whether oral immunization resulted in alterations of the microbiota and to identify whether a given microbiota composition, or subsets of the community, are associated with defined S. Typhi-specific immunological responses. The fecal microbiota composition and temporal dynamics were characterized using bacterial 16S rRNA pyrosequencing from individuals who were either immunized with the Ty21a typhoid vaccine (n = 13 or served as unvaccinated controls (n = 4. The analysis revealed considerable inter- and intra-individual variability, yet no discernible perturbations of the bacterial assemblage related to vaccine administration were observed. S. Typhi-specific cell mediated immune (CMI responses were evaluated by measurement of intracellular cytokine production using multiparametric flow cytometry, and humoral responses were evaluated by measurement of serum anti-LPS IgA and IgG titers. Volunteers were categorized according to the kinetics and magnitude of their responses. While differences in microbial composition, diversity, or temporal stability were not observed among individuals able to mount a positive humoral response, individuals displaying multiphasic CMI responses harbored more diverse, complex communities. In line with this preliminary observation, over two hundred operational taxonomic units (OTUs were found to differentiate multiphasic and late CMI responders, the vast majority of which classified within the order Clostridiales. These results provide an unprecedented view into the dramatic temporal

  17. Typing of Typhoidal Salmonella Using Extraction of Water Soluble Whole Cell Proteins and Analysing by SDS-PAGE

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    R. Yousefi Mashouf

    2005-10-01

    Full Text Available Introduction & Objective : Salmonella is one of the most important genus of Enterobacteriacea family. The aim of this study was typing of typhoidal Salmonella by SDS-PAGE and comparing the results with those of serotyping method.Materials and Methods: In this study, 4 reference strains of Salmonella species, 5 reference strains of Enterobacteriacea family and 100 clinical isolates of Salmonella that were previously collected from laboratories of Hamadan medical centers were studied. Serotyping of strains were performed by Biomereux and Difco monovalent antisera. Whole-cell proteins of strains were also separated on 10% poly acrylamide gel. Gels were stained by Coomassie Brilliant Blue and analyzed by densitometry. Results: Of 100 cases of Salmonella species, 43 cases (43% were S. typhi, 20 cases (20% were S. typhymurium, 12 cases (12% were S. para typhi B, 10 cases (10% were S. para typhi C, S. para typhi A 1 case (1% and other cases were non-typhoidal Salmonella. The results of serotyping were compared with the results obtained by SDS-PAGE. Many protein bands from 220 KDa to 18.5 KDa were detected by SDS-PAGE and they were used to differentiate the strains. S. typhi serotypes were divided into 5 sub-species and S. para typhi B and C were divided each into 3 sub-species. Protein profiles of the reference strains of Salmonella were compared with protein profiles of Enterobacteriaceae species and showed some differences in major protein bands, however, they had a very similar protein band in 43 KDa area. Conclusion: Since our data was able to divide Salmonella species to sub-types and differentiate them from Enterobacteriacea species, we concluded that analsying SDS-PAGE profile of water soluble whole-cell proteins can be used for typing of these organisms and it is comparble with serotyping, nevertheless, further researches are needed to establish SDS-PAGE method and to replace it with serotyping method.

  18. In vivo expression of Salmonella enterica serotype Typhi genes in the blood of patients with typhoid fever in Bangladesh.

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    Alaullah Sheikh

    2011-12-01

    Full Text Available BACKGROUND: Salmonella enterica serotype Typhi is the cause of typhoid fever. It is a human-restricted pathogen, and few data exist on S. Typhi gene expression in humans. METHODOLOGY/PRINCIPAL FINDINGS: We applied an RNA capture and amplification technique, Selective Capture of Transcribed Sequences (SCOTS, and microarray hybridization to identify S. Typhi transcripts expressed in the blood of five humans infected with S. Typhi in Bangladesh. In total, we detected the expression of mRNAs for 2,046 S. Typhi genes (44% of the S. Typhi genome in human blood; expression of 912 genes was detected in all 5 patients, and expression of 1,100 genes was detected in 4 or more patients. Identified transcripts were associated with the virulence-associated PhoP regulon, Salmonella pathogenicity islands, the use of alternative carbon and energy sources, synthesis and transport of iron, thiamine, and biotin, and resistance to antimicrobial peptides and oxidative stress. The most highly represented group were genes currently annotated as encoding proteins designated as hypothetical, unknown, or unclassified. Of the 2,046 detected transcripts, 1,320 (29% of the S. Typhi genome had significantly different levels of detection in human blood compared to in vitro cultures; detection of 141 transcripts was significantly different in all 5 patients, and detection of 331 transcripts varied in at least 4 patients. These mRNAs encode proteins of unknown function, those involved in energy metabolism, transport and binding, cell envelope, cellular processes, and pathogenesis. We confirmed increased expression of a subset of identified mRNAs by quantitative-PCR. CONCLUSIONS/SIGNIFICANCE: We report the first characterization of bacterial transcriptional profiles in the blood of patients with typhoid fever. S. Typhi is an important global pathogen whose restricted host range has greatly inhibited laboratory studies. Our results suggest that S. Typhi uses a largely

  19. Identification by PCR of non-typhoidal Salmonella enterica serovars associated with invasive infections among febrile patients in Mali.

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    Sharon M Tennant

    Full Text Available BACKGROUND: In sub-Saharan Africa, non-typhoidal Salmonella (NTS are emerging as a prominent cause of invasive disease (bacteremia and focal infections such as meningitis in infants and young children. Importantly, including data from Mali, three serovars, Salmonella enterica serovar Typhimurium, Salmonella Enteritidis and Salmonella Dublin, account for the majority of non-typhoidal Salmonella isolated from these patients. METHODS: We have extended a previously developed series of polymerase chain reactions (PCRs based on O serogrouping and H typing to identify Salmonella Typhimurium and variants (mostly I 4,[5],12:i:-, Salmonella Enteritidis and Salmonella Dublin. We also designed primers to detect Salmonella Stanleyville, a serovar found in West Africa. Another PCR was used to differentiate diphasic Salmonella Typhimurium and monophasic Salmonella Typhimurium from other O serogroup B, H:i serovars. We used these PCRs to blind-test 327 Salmonella serogroup B and D isolates that were obtained from the blood cultures of febrile patients in Bamako, Mali. PRINCIPAL FINDINGS: We have shown that when used in conjunction with our previously described O-serogrouping PCR, our PCRs are 100% sensitive and specific in identifying Salmonella Typhimurium and variants, Salmonella Enteritidis, Salmonella Dublin and Salmonella Stanleyville. When we attempted to differentiate 171 Salmonella Typhimurium (I 4,[ 5],12:i:1,2 strains from 52 monophasic Salmonella Typhimurium (I 4,[5],12:i:- strains, we were able to correctly identify 170 of the Salmonella Typhimurium and 51 of the Salmonella I 4,[5],12:i:- strains. CONCLUSION: We have described a simple yet effective PCR method to support surveillance of the incidence of invasive disease caused by NTS in developing countries.

  20. A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.

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    Christiane Dolecek

    Full Text Available BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day versus azithromycin (20 mg/kg/day as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi. PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin, (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]. Overall treatment failure occurred in 13/145 (9% patients in the gatifloxacin group and 13/140 (9.3% patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]. 96% (254/263 of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263 were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the

  1. Typhoid intestinal perforations at a University teaching hospital in Northwestern Tanzania: A surgical experience of 104 cases in a resource-limited setting

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    Chalya Phillipo L

    2012-03-01

    Full Text Available Abstract Background Typhoid intestinal perforation is still prevalent in many developing countries. Despite the advances in the management, the outcome in these patients in resource limited countries is still very poor. This study was to review our experiences on the surgical management of typhoid intestinal perforation and to determine the prognostic factors for mortality in our local setting. Methods This was a combined retrospective and prospective study of patients who were operated for typhoid intestinal perforation at Bugando Medical Centre between August 2006 and September 2011. Data collected were analyzed using SPSS computer software version 15. Results A total of 104 patients were studied representing 8.7% of typhoid fever cases. Males were affected twice more than the females (2.6:1. Their ages ranged from 8 to 76 years with a median age of 18.5 years. The peak age incidence was in the 11-20 years age group. Fever and abdominal pain were the most common presenting symptoms and majority of the patients (80.8% perforated between within 14 days of illness. Chest and abdominal radiographs revealed pneumoperitonium in 74.7% of cases. Ultrasound showed free peritoneal collection in 85.7% of cases. Nine (10.2% patients were HIV positive with a median CD4+ count of 261 cells/μl. The perforation-surgery interval was more than 72 hours in 90(86.5% patients. The majority of patients (84.6% had single perforations and ileum was the most common part of the bowel affected occurring in 86.2% of cases. Simple closure of the perforations was the most commonly performed procedure accounting for 78.8% of cases. Postoperative complication rate was 39.4% and surgical site infection was the most frequent complication in 55.5% of cases. Mortality rate was 23.1% and it was statistically significantly associated with delayed presentation, inadequate antibiotic treatment prior to admission, shock on admission, HIV positivity, low CD4 count (P Conclusion

  2. Head-to-head comparison of humoral immune responses to Vi capsular polysaccharide and Salmonella Typhi Ty21a typhoid vaccines--a randomized trial.

    Directory of Open Access Journals (Sweden)

    Anu Kantele

    Full Text Available 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

  3. Host response transcriptional profiling reveals extracellular components and ABC (ATP-binding cassette transporters gene enrichment in typhoid fever-infected Nigerian children

    Directory of Open Access Journals (Sweden)

    Resau James H

    2011-09-01

    Full Text Available Abstract Background Salmonella enterica serovar Typhi (S. Typhi is a human-specific pathogen that causes typhoid fever, and remains a global health problem especially in developing countries. Its pathogenesis is complex and host response is poorly understood. In Africa, typhoid fever can be a major cause of morbidity in young infected children. The onset of the illness is insidious and clinical diagnosis is often unreliable. Gold standard blood culture diagnostic services are limited, thus rapid, sensitive, and affordable diagnostic test is essential in poor-resourced clinical settings. Routine typhoid fever vaccination is highly recommended but currently licensed vaccines provide only 55-75% protection. Recent epidemiological studies also show the rapid emergence of multi-drug resistant S. Typhi strains. High-throughput molecular technologies, such as microarrays, can dissect the molecular mechanisms of host responses which are S. Typhi-specific to provide a comprehensive genomic component of immunological responses and suggest new insights for diagnosis and treatment. Methods Global transcriptional profiles of S. Typhi-infected young Nigerian children were obtained from their peripheral blood and compared with that of other bacteremic infections using Agilent gene expression microarrays. The host-response profiles of the same patients in acute vs. convalescent phases were also determined. The top 96-100 differentially-expressed genes were identified and four genes were validated by quantitative real-time PCR. Gene clusters were obtained and functional pathways were predicted by DAVID (Database for Annotation, Visualization and Integrated Discovery. Results Transcriptional profiles from S. Typhi-infected children could be distinguished from those of other bacteremic infections. Enriched gene clusters included genes associated with extracellular peptides/components such as lipocalin (LCN2 and systemic immune response which is atypical in

  4. Murine antigen-induced arthritis.

    NARCIS (Netherlands)

    Berg, W.B. van den; Joosten, L.A.B.; Lent, P.L.E.M. van

    2007-01-01

    Antigen induced arthritis is a unilateral T-cell driven model caused by direct injection of an antigen into the knee joint of a FCA preimmunized animal. The chronicity is determined by antigen retention in avascular structures of the joint through charge mediated binding or antibody mediated trappin

  5. Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model.

    Directory of Open Access Journals (Sweden)

    Monica A McArthur

    2015-05-01

    Full Text Available Salmonella Typhi (S. Typhi, the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (Treg by flow and mass cytometry using specimens obtained from a human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating Treg between volunteers diagnosed with typhoid (TD and those who were not (No TD. TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with Treg homing to the gut. Additionally, S. Typhi-specific Treg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1. We further demonstrate that depletion of Treg results in increased S. Typhi-specific cytokine production by CD8+ TEM in vitro. These results suggest that the tissue distribution of activated Treg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases.

  6. Antimicrobial resistance in invasive non-typhoid Salmonella from the Democratic Republic of the Congo : emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases

    OpenAIRE

    Octavie Lunguya; Veerle Lejon; Marie-France Phoba; Sophie Bertrand; Raymond Vanhoof; Youri Glupczynski; Jan Verhaegen; Jean-Jacques Muyembe-Tamfum; Jan Jacobs

    2013-01-01

    Background: Co-resistance against the first-line antibiotics ampicillin, chloramphenicol and trimethoprim/sulphamethoxazole or multidrug resistance (MDR) is common in non typhoid Salmonella (NTS). Use of alternative antibiotics, such as fluoroquinolones or third generation cephalosporins is threatened by increasing resistance, but remains poorly documented in Central-Africa. Methodology/Principal findings: As part of a microbiological surveillance study in DR Congo, blood cultures were collec...

  7. Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

    OpenAIRE

    Mooney, Jason P.; Lee, Seung-Joo; Lokken, Kristen L.; Nanton, Minelva R.; Nuccio, Sean-Paul; Stephen J McSorley; Tsolis, Renée M.

    2015-01-01

    In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonletha...

  8. Apoptosis in irradiated murine tumors.

    Science.gov (United States)

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors.

  9. Apoptosis in irradiated murine tumors.

    Science.gov (United States)

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors. PMID:1886987

  10. Review on studies of disease burden of typhoid and paratyphoid fever%伤寒、副伤寒疾病负担研究现状

    Institute of Scientific and Technical Information of China (English)

    张莹; 张静

    2011-01-01

    国内外关于伤寒、副伤寒的疾病负担研究,大多从疾病流行病学负担方面进行评价,仅有少量有关伤寒疫苗的研究从成本效果方面进行深入的分析,认为在伤寒中高流行地区开展普遍的疫苗接种有较好的成本效果,在这些地区把伤寒疫苗纳入免疫规划具有重要意义.本文通过对国内外研究现状进行综合描述,以期为我国伤寒、副伤寒疾病的负担评价提供参考.%Many countries have developed researches about disease burden of enteric fever. Most of the studies provided the estimated epidemiological burden. However, only a few of the studies finished and gave the economic burden and epidemiological data to evaluate the cost-effectivenss of vaccination against typhoid in Asian. The immune programs of typhoid fever were considered as very cost-effective. So it is worth putting typhoid vaccines in vaccination programs in those countries with moderate-to-high endemic. This review aims to provide reference for evaluating burden of enteric fever in china.

  11. Evaluation of immune responses to an oral typhoid vaccine, Ty21a, in children from 2 to 5 years of age in Bangladesh.

    Science.gov (United States)

    Bhuiyan, Taufiqur R; Choudhury, Feroza K; Khanam, Farhana; Saha, Amit; Sayeed, Md Abu; Salma, Umme; Lundgren, Anna; Sack, David A; Svennerholm, Ann-Mari; Qadri, Firdausi

    2014-02-19

    Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years. We studied immune responses to a liquid formulation of Ty21a in children 2-5 years of age. Since children in developing countries are in general hypo responsive to oral vaccines, the study was designed to determine if anti-helminthic treatment prior to vaccination, improves responses. In a pilot study in 20 children aged 4-5 years, the immune responses in plasma and in antibody in lymphocyte secretions (ALS) to the enteric coated capsule formulation of Ty21a was found to be comparable to a liquid formulation (P>0.05). Based on this, children (n=252) aged ≥ 2-vaccine was well tolerated with only a few mild adverse events recorded in vaccine are carried out in children under five, including those less than two years of age to determine if Ty21a is protective in these age groups and applicable as a public health tool for controlling typhoid fever in high prevalence areas of typhoid fever including Bangladesh.

  12. Immune responses to Vi capsular polysaccharide typhoid vaccine in children 2 to 16 years old in Karachi, Pakistan, and Kolkata, India.

    Science.gov (United States)

    Ochiai, R Leon; Khan, M Imran; Soofi, Sajid B; Sur, Dipika; Kanungo, Suman; You, Young A; Habib, M Atif; Sahito, Shah Muhammad; Manna, Byomkesh; Dutta, Shanta; Acosta, Camilo J; Ali, Mohammad; Bhattacharya, Sujit K; Bhutta, Zulfiqar A; Clemens, John D

    2014-05-01

    The geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 μg of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.

  13. SuperSILAC Quantitative Proteome Profiling of Murine Middle Ear Epithelial Cell Remodeling with NTHi.

    Directory of Open Access Journals (Sweden)

    Stéphanie Val

    Full Text Available Chronic Otitis Media with effusion (COME develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Non-typeable Haemophilus influenzae (NTHi, the most common acute Otitis Media (OM pathogen, is postulated to promote middle ear epithelial remodeling in the progression of OM from acute to chronic. The goals of this study were to examine histopathological and quantitative proteomic epithelial effects of NTHi challenge in a murine middle ear epithelial cell line.NTHi lysates were generated and used to stimulate murine epithelial cells (mMEEC cultured at air-liquid interface over 48 hours- 1 week. Conditional quantitative Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC of cell lysates was performed to interrogate the global protein production in the cells, using the SuperSILAC technique. Histology of the epithelium over time was done to measure bacterial dependent remodeling.Mass spectrometry analysis identified 2,565 proteins across samples, of which 74 exhibited differential enrichment or depletion in cell lysates (+/-2.0 fold-change; p value<0.05. The key molecular functions regulated by NTHi lysates exposure were related to cell proliferation, death, migration, adhesion and inflammation. Finally, chronic exposure induced significant epithelial thickening of cells grown at air liquid interface.NTHi lysates drive pathways responsible of cell remodeling in murine middle ear epithelium which likely contributes to observed epithelial hyperplasia in vitro. Further elucidation of these mediators will be critical in understanding the progression of OM from acute to chronic at the molecular level.

  14. Restoration of Pattern Recognition Receptor Costimulation to Treat Chromoblastomycosis, a Chronic Fungal Infection of the Skin

    OpenAIRE

    da Glória Sousa, Maria; Reid, Delyth M.; Schweighoffer, Edina; Tybulewicz, Victor; Ruland, Jürgen; Langhorne, Jean; Yamasaki, Sho; Taylor, Philip R.; Almeida, Sandro R.; Brown, Gordon D.

    2011-01-01

    Summary Chromoblastomycosis is a chronic skin infection caused by the fungus Fonsecaea pedrosoi. Exploring the reasons underlying the chronic nature of F. pedrosoi infection in a murine model of chromoblastomycosis, we find that chronicity develops due to a lack of pattern recognition receptor (PRR) costimulation. F. pedrosoi was recognized primarily by C-type lectin receptors (CLRs), but not by Toll-like receptors (TLRs), which resulted in the defective induction of proinflammatory cytokines...

  15. Structural basis of typhoid: Salmonella typhi type IVb pilin (PiLS) and cystic fibrosis transmembrane conductance regulator interaction

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishna, A.M.; Saxena, A.; Mok, H. Y.-K.; Swaminathan, K.

    2009-11-01

    The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein ({Delta}PilS), which makes the pilus, was determined at 1.9 {angstrom} resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of {Delta}PilS and a target CFTR peptide, determined at 1.8 {angstrom}, confirms that residues 113-117 (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.

  16. Structural Basis of Typhoid: Salmonella typhi Type IVb pilin (PilS) and Cystic Fibrosis Transmembrane Conductance Regulatory Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishna, A.; Saxena, A; Mok, H; Swaminathan, K

    2009-01-01

    The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein (PilS), which makes the pilus, was determined at 1.9 A resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of PilS and a target CFTR peptide, determined at 1.8 A, confirms that residues 113-117 (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.

  17. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

    DEFF Research Database (Denmark)

    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    , the kdgR-SNP was confirmed to confer selective advantage during chronic infections and constitute a true patho-adaptive mutation. Together, the results provide evidence for rapid genetic adaptation to the host of S. Typhimurium and validate experimental evolution in the context of host infection......Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S...... type strains of S. Typhimurium 4/74 were used to establish chronic infections of 129X1/SvJ mice. Over the course of infections, S. Typhimurium bacteria were isolated from feces and from livers and spleens upon termination of the experiment. In all samples dominant clones were identified and select...

  18. Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma

    OpenAIRE

    Oliveira, Tatiane Teixeira; Campos, Keina Maciele; Cerqueira-Lima, Ana Tereza; Cana Brasil Carneiro, Tamires; da Silva Velozo, Eudes; Ribeiro Melo, Ingrid Christie Alexandrino; Figueiredo, Eugênia Abrantes; de Jesus Oliveira, Eduardo; de Vasconcelos, Darizy Flávia Silva Amorim; Pontes-de-Carvalho, Lain Carlos; Alcântara-Neves, Neuza Maria; Figueiredo, Camila Alexandrina

    2015-01-01

    Background Asthma is an inflammatory condition characterized by airway hyperresponsiveness and chronic inflammation. The resolution of inflammation is an essential process to treat this condition. In this study we investigated the effect of Allium cepa L. extract (AcE) and quercetin (Qt) on cytokine and on smooth muscle contraction in vitro and its therapeutic potential in a murine model of asthma. Methods AcE was obtained by maceration of Allium cepa L. and it was standardized in terms of qu...

  19. Epidemiology of Non-Typhoidal Salmonella (NTS in Humans and Animals in the Gambia and Senegal

    Directory of Open Access Journals (Sweden)

    Dione, M.

    2010-01-01

    Full Text Available Non-Typhoidal Salmonella (NTS species are important food-borne pathogens. Although acute gastroenteritis is the most common clinical symptom, complications can occur resulting in bacteraemia with or without focal infections. Food products, especially food of animal origin such as poultry are associated with the transmission to humans. In Africa, NTS are among the most common cause of bloodstream infections in children younger than 5 years. Epidemiological data on NTS are lacking in Africa both for human and animal infections. Therefore, a study providing a better understanding of the factors that lead to the emergence of NTS is a prerequisite for the design of improved intervention strategies to control these pathogens. The aim of this thesis was to study the epidemiology of NTS pathogens in humans and animals in The Gambia and Senegal. Chapter 1 reviews the current status of knowledge on NTS infections in Africa with focus on The Gambia and Senegal. It also provides the background against which these studies were conducted. Chapter 2 describes the prevalence of NTS along the poultry production chain in Casamance, Senegal. Fifty seven randomly selected broiler farms, 42 street restaurants and 285 chicken carcasses were studied. The following farm prevalences were reported: 35.1, 38.6 and 29.8% in chicken faeces, on carcass skin, and in muscles, respectively. NTS were found in chicken meat servings of 14.3% of the 42 street restaurants and in 40.4% of the 285 chicken carcasses examined. The most prevalent serotypes among the eighteen identified were Salmonella Brancaster (57.9%, Salmonella Goelzau (10.7%, Salmonella Kentucky (8.4%, and Salmonella Hadar (7.3%. The following serotypes were for the first time identified in Senegal: Salmonella Bandia, Salmonella Bessi, Salmonella Brunei, Salmonella Hull, Salmonella Istanbul, Salmonella Javiana, Salmonella Magherafelt, Salmonella Molade, Salmonella oxford, Salmonella Poona, Salmonella Rubislaw

  20. Murine Typhus in Child, Yucatan, Mexico

    OpenAIRE

    Zavala-Castro, Jorge E.; Zavala-Velázquez, Jorge E.; Uicab, Justo Eduardo Sulú

    2009-01-01

    A case of murine typhus in Yucatan was diagnosed in a child with nonspecific signs and symptoms. The finding of Rickettsia typhi increases the number of Rickettsia species identified in Yucatan and shows that studies are needed to determine the prevalence and incidence of rickettsioses in Mexico.

  1. Reemergence of Murine Typhus in the US

    Centers for Disease Control (CDC) Podcasts

    2015-04-21

    Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

  2. Structure of the murine Thy-1 gene

    NARCIS (Netherlands)

    V. Giguere; K-I. Isobe; F.G. Grosveld (Frank)

    1985-01-01

    textabstractWe have cloned the murine Thy-1.1 (AKR) and Thy-1.2 (Balb/c) genes. The complete exon/intron structure and the nucleotide sequence of the Thy-1.2 gene was determined. The gene contains four exons and three intervening sequences. The complete transcriptional unit gives rise to a tissue an

  3. [Chronicity, chronicization, systematization of delusions].

    Science.gov (United States)

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

  4. Assessment of carbon nanoparticle exposure on murine macrophage function

    Science.gov (United States)

    Suro-Maldonado, Raquel M.

    There is growing concern about the potential cytotoxicity of nanoparticles. Exposure to respirable ultrafine particles (2.5uM) can adversely affect human health and have been implicated with episodes of increased respiratory diseases such as asthma and allergies. Nanoparticles are of particular interest because of their ability to penetrate into the lung and potentially elicit health effects triggering immune responses. Nanoparticles are structures and devises with length scales in the 1 to 100-nanometer range. Black carbon (BC) nanoparticles have been observed to be products of combustion, especially flame combustion and multi-walled carbon nanotubes (MWCNT) have been shown to be found in both indoor and outdoor air. Furthermore, asbestos, which have been known to cause mesothelioma as well as lung cancer, have been shown to be structurally identical to MWCNTs. The aims of these studies were to examine the effects of carbon nanoparticles on murine macrophage function and clearance mechanisms. Macrophages are immune cells that function as the first line of defense against invading pathogens and are likely to be amongst the first cells affected by nanoparticles. Our research focused on two manufactured nanoparticles, MWCNT and BC. The two were tested against murine-derived macrophages in a chronic contact model. We hypothesized that long-term chronic exposure to carbon nanoparticles would decrease macrophages ability to effectively respond to immunological challenge. Production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), cell surface macrophage; activation markers, reactive oxygen species formation (ROS), and antigen processing and presentation were examined in response to lipopolysaccharide (LPS) following a 144hr exposure to the particulates. Data demonstrated an increase in TNF-alpha, and NO production; a decrease in phagocytosis and antigen processing and presentation; and a decrease in the expression levels of cell surface macrophage

  5. Interplay of Murine Gammaherpesvirus 68 with NF-kappaB Signaling of the Host.

    Science.gov (United States)

    Cieniewicz, Brandon; Santana, Alexis L; Minkah, Nana; Krug, Laurie T

    2016-01-01

    Herpesviruses establish a chronic infection in the host characterized by intervals of lytic replication, quiescent latency, and reactivation from latency. Murine gammaherpesvirus 68 (MHV68) naturally infects small rodents and has genetic and biologic parallels with the human gammaherpesviruses (gHVs), Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. The murine gammaherpesvirus model pathogen system provides a platform to apply cutting-edge approaches to dissect the interplay of gammaherpesvirus and host determinants that enable colonization of the host, and that shape the latent or lytic fate of an infected cell. This knowledge is critical for the development of novel therapeutic interventions against the oncogenic gHVs. The nuclear factor kappa B (NF-κB) signaling pathway is well-known for its role in the promotion of inflammation and many aspects of B cell biology. Here, we review key aspects of the virus lifecycle in the host, with an emphasis on the route that the virus takes to gain access to the B cell latency reservoir. We highlight how the murine gammaherpesvirus requires components of the NF-κB signaling pathway to promote replication, latency establishment, and maintenance of latency. These studies emphasize the complexity of gammaherpesvirus interactions with NF-κB signaling components that direct innate and adaptive immune responses of the host. Importantly, multiple facets of NF-κB signaling have been identified that might be targeted to reduce the burden of gammaherpesvirus-associated diseases. PMID:27582728

  6. 左氧氟沙星治疗儿童伤寒分析%Efficacy of Levofloxacin in the Treatment of Typhoid Fever Children

    Institute of Scientific and Technical Information of China (English)

    王永

    2015-01-01

    Objective To study the clinical effect of levofloxacin treatment of typhoid fever in children,provide a reliable basis for the clinical treatment of these diseases.Methods A total of 38 cases with typhoid fever cases were analyzed retrospectively from 2008 to 2011 in our hospital,all the children were taking levofloxacin treatment.Results After treatment of using levofloxacin,headache,vomiting,nausea, fever,cough symptoms have been greatly improved. Clinical significent effective rate was 25.38%,effective rate was 66.73%,total effective rate was 92.11%.Conclusion The treatment effect with levofloxacin for children typhoid is good,can be used in clinical as an excellent way for children typhoid fever. The follow-up study of the medical records of six months to a year,there is no joint lameness,pain and other cases of the disease.%目的:研究分析左氧氟沙星对儿童伤寒治疗的临床效果,为临床治疗该类疾病提供可靠的依据。方法2008年~2011年我院共对38例伤寒儿童病例进行了回顾分析,全部患儿临床中都采取左氧氟沙星治疗。结果临床中儿童使用左氧氟沙星治疗后,其头痛、呕吐、恶心、发热、咳嗽的症状都有了很大的改善,临床治疗显效率是25.38%,有效率是66.73%,治疗总有效率是92.11%。结论儿童伤寒使用左氧氟沙星治疗的效果比较优秀,临床中可以作为儿童伤寒治疗的一种优秀方式使用,对此次研究病历进行随访半年至一年中,没有出现关节跛行、疼痛等病例。

  7. Differences in Clinical and Laboratory Findings between Group D and Non-Group D Non-Typhoidal Salmonella Gastroenteritis in Children

    OpenAIRE

    Park, Heung Keun; Rhie, Kyuyol; Yeom, Jung Sook; Park, Ji Sook; Park, Eun Sil; Seo, Ji-Hyun; Lim, Jae Young; Park, Chan-Hoo; Woo, Hyang-Ok; Youn, Hee-Shang; Kang, Ki Ryeon; Park, Jung Je

    2015-01-01

    Purpose To investigate the differences in clinical features and laboratory findings between group D and non-group D non-typhoidal Salmonella (NTS) gastroenteritis in children. Methods A retrospective chart review of children diagnosed with NTS confirmed by culture study was performed. The clinical features and laboratory findings of group D and non-group D NTS were compared. Results From 2003 to 2012, 75 cases were diagnosed as NTS at our center. The number of group D and non-group D patients...

  8. Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study.

    Science.gov (United States)

    Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna

    2016-04-01

    Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

  9. An Outbreak of Food-Borne Typhoid Fever Due to Salmonella enterica Serotype Typhi in Japan Reported for the First Time in 16 Years

    Science.gov (United States)

    Kobayashi, Tetsuro; Kutsuna, Satoshi; Hayakawa, Kayoko; Kato, Yasuyuki; Ohmagari, Norio; Uryu, Hideko; Yamada, Ritsuko; Kashiwa, Naoyuki; Nei, Takahito; Ehara, Akihito; Takei, Reiko; Mori, Nobuaki; Yamada, Yasuhiro; Hayasaka, Tomomi; Kagawa, Narito; Sugawara, Momoko; Suzaki, Ai; Takahashi, Yuno; Nishiyama, Hiroyuki; Morita, Masatomo; Izumiya, Hidemasa; Ohnishi, Makoto

    2016-01-01

    For the first time in 16 years, a food-borne outbreak of typhoid fever due to Salmonella enterica serotype Typhi was reported in Japan. Seven patients consumed food in an Indian buffet at a restaurant in the center of Tokyo, while one was a Nepali chef in the restaurant, an asymptomatic carrier and the implicated source of this outbreak. The multiple-locus variable-number tandem repeat analysis showed 100% consistency in the genomic sequence for five of the eight cases. PMID:26621565

  10. Characterization of extended-spectrum β-lactamase (ESBL) producing non-typhoidal Salmonella (NTS) from imported food products.

    Science.gov (United States)

    Bae, Dongryeoul; Cheng, Chorng-Ming; Khan, Ashraf A

    2015-12-01

    Food contaminated with extended-spectrum β-lactamase (ESBL)-producing Salmonella enterica has emerged as an important global issue due to the international food-product trade. Therefore, the purpose of this study was to investigate whether imported food products can serve as a reservoir for non-typhoidal Salmonella (NTS) that can transmit β-lactam-resistance to humans through ingestion of the contaminated food. NTS isolates (n=110) were collected from various imported food products (n=3480) from 2011 to 2013. The NTS isolates were analyzed by serotyping, antimicrobial susceptibility tests, and plasmid profiling. Salmonella ser. Weltevreden, Salmonella ser. Newport, Salmonella ser. Senftenberg, Salmonella ser. Virchow, Salmonella ser. Enteritidis, Salmonella ser. Typhimurium, and Salmonella ser. Bareilly were the most prevalent serovars. Nine NTS strains were resistant to ampicillin and/or one or more cephalosporins (MIC>32 μg/mL). Polymerase chain reaction (PCR) detection revealed that all nine isolates carried the bla(TEM-1) β-lactamase gene, with or without the bla(CTX-M-9) or bla(OXA-1) genes. Two isolates, PSS_913 and PSS_988, exhibited decreased susceptibility to extended-spectrum cephalosporins and ampicillin. Plasmids ranging in size from less than 8 to over 165 kbp, from all of the 9 resistant isolates, belonged to the IncHI1, IncI1, IncN, or IncX groups. Conjugation experiments and Southern hybridization, using bla(TEM-1), confirmed the plasmid-mediated transfer of ESBL genes, which resulted in increased MICs of β-lactams for Escherichia coli transconjugants. The contamination of imported food products by NTS with conjugative plasmid-borne ESBL genes may contribute to the spread of ESBL-producing NTS and compromise the therapeutic activity of extended-spectrum β-lactam antibiotics.

  11. Cross-reactive immune response induced by the Vi capsular polysaccharide typhoid vaccine against Salmonella Paratyphi strains.

    Science.gov (United States)

    Pakkanen, S H; Kantele, J M; Kantele, A

    2014-03-01

    There are no vaccines in clinical use against paratyphoid fever, caused by Salmonella Paratyphi A and B or, rarely, C. Oral Salmonella Typhi Ty21a typhoid vaccine elicits a significant cross-reactive immune response against S. Paratyphi A and B, and some reports suggest cross-protective efficacy against the disease. These findings are ascribed to the O-12 antigen shared between the strains. The Vi capsular polysaccharide vaccine has been shown to elicit antibodies reactive with O-9,12. Twenty-five volunteers immunized with the parenteral Vi vaccine (Typherix(®) ) were explored for plasmablasts cross-reactive with paratyphoid strains; the responses were compared to those in 25 age- and gender-matched volunteers immunized with Ty21a (Vivotif(®) ). Before vaccination, 48/50 vaccinees had no plasmablasts reactive with the antigens. Seven days after vaccination, 15/25 and 22/25 Vi- and Ty21a-vaccinated volunteers had circulating plasmablasts producing antibodies cross-reactive with S. Paratyphi A, 18/25 and 23/25 with S. Paratyphi B and 16/25 and 9/25 with Paratyphi C, respectively. Compared to the Ty21a group, the Vi group showed significantly lower responses to S. Paratyphi A and B and higher to S. Paratyphi C. To conclude, the Vi vaccine elicited a cross-reactive plasmablast response to S. Paratyphi C (Vi antigen in common) and less marked responses to S. Paratyphi A and B than the Ty21a preparation. S. Paratyphi A and B both being Vi-negative, the result can be explained by trace amounts of bacterial cell wall O-12 antigen in the Vi preparation, despite purification. The clinical significance of this finding remains to be determined.

  12. Retroviral Transduction of Murine Primary T Lymphocytes

    Science.gov (United States)

    Lee, James; Sadelain, Michel; Brentjens, Renier

    2016-01-01

    Summary In comparison to human T cells, efficient retroviral gene transfer and subsequent expansion of murine primary T cells is more difficult to achieve. Herein, we describe an optimized gene transfer protocol utilizing an ecotropic viral vector to transduce primary murine T cells activated with magnetic beads coated with agonistic anti-CD3 and CD28 antibodies. Activated T cells are subsequently centrifuged (spinoculated) on RetroNectin-coated tissue culture plates in the context of retroviral supernatant. Variables found to be critical to high gene transfer and subsequent efficient T cell expansion included CD3/CD28 magnetic bead to cell ratio, time from T cell activation to initial spinoculation, frequency of T cell spinoculation, interleukin-2 concentration in the medium, and the initial purity of the T cell preparation. PMID:19110621

  13. Advances in Murine Models of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Li-li Kong

    2013-01-01

    Full Text Available Diabetic nephropathy (DN is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN.

  14. Immunodetection of Murine Lymphotoxins in Eukaryotic Cells.

    Science.gov (United States)

    Boitchenko, Veronika E.; Korobko, Vyacheslav G.; Prassolov, Vladimir S.; Kravchenko, Vladimir V.; Kuimov, Alexander N.; Turetskaya, Regina L.; Kuprash, Dmitry V.; Nedospasov, Sergei A.

    2000-10-01

    Lymphotoxins alpha and beta (LTalpha and LTbeta) are members of tumor necrosis factor superfamily. LT heterotrimers exist on the surface of lymphocytes and signal through LTbeta receptor while soluble LTalpha homotrimer can signal through TNF receptors p55 and p75. LT-, as well as TNF-mediated signaling are important for the organogenesis and maintenance of microarchitecture of secondary lymphoid organs in mice and has been implicated in the mechanism of certain inflammatory syndromes in humans. In this study we describe the generation of eukaryotic expression plasmids encoding murine LTalpha and LTbeta genes and a prokaryotic expression construct for murine LTalpha. Using recombinant proteins expressed by these vectors as tools for antisera selection, we produced and characterized several polyclonal antibodies capable of detecting LT proteins in eukaryotic cells.

  15. Chronic cholecystitis

    Science.gov (United States)

    ... foods may relieve symptoms in people. However, the benefit of a low-fat diet has not been proven. Alternative Names Cholecystitis - chronic Images Cholecystitis, CT scan Cholecystitis, cholangiogram Cholecystolithiasis Gallstones, cholangiogram Cholecystogram References Wang ...

  16. Chronic Meningitis

    Science.gov (United States)

    ... School Lunch Lines FDA Cracks Down on Antibacterial Soaps Health Tip: Schedule a Back-to-School Dental ... the Professional Version Meningitis Introduction to Meningitis Acute Bacterial Meningitis Viral Meningitis Noninfectious Meningitis Recurrent Meningitis Chronic ...

  17. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  18. Eliminating Murine Norovirus by Cross-Fostering

    OpenAIRE

    Buxbaum, Laurence U.; DeRitis, Pierina C.; Chu, Niansheng; Conti, Pierre A.

    2011-01-01

    Murine norovirus (MNV) is a newly discovered and extremely prevalent pathogen of laboratory mouse colonies. MNV causes severe disease in some immunocompromised mouse strains and can cause persistent infections even in immunocompetent mice. Despite the fact that immunocompetent mice are generally asymptomatic, the possibility that MNV infection might alter immune responses makes its eradication a potentially useful goal for many facilities. Initial attempts by others to use a strategy of testi...

  19. [Isolation of a highly purified capsular polysaccharide from Salmonella enterica serovar Typhi (Salmonella typhi)--Vi-antigen and its use in serological diagnosis of typhoid fever].

    Science.gov (United States)

    Tesheva, A M; Aparin, P G; L'vov, V L

    2002-01-01

    For use in differential diagnostics of typhoid fever, samples of the capsular polysaccharide from Salmonella enterica serovar Typhi (usually named Vi-antigen) were isolated and characterized by physicochemical and serological methods. It was shown that only the sample of Vi-antigen with the minimal (0.57%) admixture of the corresponding lipopolysaccharide (LPS) from S. typhi retained a high serological activity in the tests with monoreceptor anti-Vi sera. However, it exhibited a substantially weaker reaction with sera from normal donors and patients with acute nontyphoid salmonelloses, than Vi-antigen preparations with a higher (0.8-1.2%) LPS content. The chromatographically pure Vi-antigen was purified by triple reprecipitation with hexadecyltrimethylammonium bromide. The content of the LPS admixture in the resulting Vi-antigen samples was quantitatively determined by GC. A high purification level of the Vi-antigen from the LPS admixture allows us to hope that this preparation could serve as a basic component of the test system for the diagnostics of typhoid fever. The English version of the paper.

  20. Osteoarticular tissue infection and development of skeletal pathology in murine brucellosis

    Directory of Open Access Journals (Sweden)

    Diogo M. Magnani

    2013-05-01

    Brucellosis, a frequent bacterial zoonosis, can produce debilitating chronic disease with involvement of multiple organs in human patients. Whereas acute brucellosis is well studied using the murine animal model, long-term complications of host-pathogen interaction remain largely elusive. Human brucellosis frequently results in persistent, chronic osteoarticular system involvement, with complications such as arthritis, spondylitis and sacroiliitis. Here, we focused on identifying infectious sites in the mouse that parallel Brucella melitensis foci observed in patients. In vivo imaging showed rapid bacterial dispersal to multiple sites of the murine axial skeleton. In agreement with these findings, immunohistochemistry revealed the presence of bacteria in bones and limbs, and in the lower spine vertebrae of the axial skeleton where they were preferentially located in the bone marrow. Surprisingly, some animals developed arthritis in paws and spine after infection, but without obvious bacteria in these sites. The identification of Brucella in the bones of mice corroborates the findings in humans that these osteoarticular sites are important niches for the persistence of Brucella in the host, but the mechanisms that mediate pathological manifestations in these sites remain unclear. Future studies addressing the immune responses within osteoarticular tissue foci could elucidate important tissue injury mediators and Brucella survival strategies.

  1. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    International Nuclear Information System (INIS)

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

  2. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  3. Genomic Comparison of Non-Typhoidal Salmonella enterica Serovars Typhimurium, Enteritidis, Heidelberg, Hadar and Kentucky Isolates from Broiler Chickens.

    Directory of Open Access Journals (Sweden)

    Akhilesh S Dhanani

    Full Text Available Non-typhoidal Salmonella enterica serovars, associated with different foods including poultry products, are important causes of bacterial gastroenteritis worldwide. The colonization of the chicken gut by S. enterica could result in the contamination of the environment and food chain. The aim of this study was to compare the genomes of 25 S. enterica serovars isolated from broiler chicken farms to assess their intra- and inter-genetic variability, with a focus on virulence and antibiotic resistance characteristics.The genomes of 25 S. enterica isolates covering five serovars (ten Typhimurium including three monophasic 4,[5],12:i:, four Enteritidis, three Hadar, four Heidelberg and four Kentucky were sequenced. Most serovars were clustered in strongly supported phylogenetic clades, except for isolates of serovar Enteritidis that were scattered throughout the tree. Plasmids of varying sizes were detected in several isolates independently of serovars. Genes associated with the IncF plasmid and the IncI1 plasmid were identified in twelve and four isolates, respectively, while genes associated with the IncQ plasmid were found in one isolate. The presence of numerous genes associated with Salmonella pathogenicity islands (SPIs was also confirmed. Components of the type III and IV secretion systems (T3SS and T4SS varied in different isolates, which could explain in part, differences of their pathogenicity in humans and/or persistence in broilers. Conserved clusters of genes in the T3SS were detected that could be used in designing effective strategies (diagnostic, vaccination or treatments to combat Salmonella. Antibiotic resistance genes (CMY, aadA, ampC, florR, sul1, sulI, tetAB, and srtA and class I integrons were detected in resistant isolates while all isolates carried multidrug efflux pump systems regardless of their antibiotic susceptibility profile.This study showed that the predominant Salmonella serovars in broiler chickens harbor genes

  4. Neuropathological Changes and Clinical Features of Autism Spectrum Disorder Participants Are Similar to that Reported in Congenital and Chronic Cerebral Toxoplasmosis in Humans and Mice

    Science.gov (United States)

    Prandota, Joseph

    2010-01-01

    Anatomic, histopathologic, and MRI/SPET studies of autistic spectrum disorders (ASD) patients' brains confirm existence of very early developmental deficits. In congenital and chronic murine toxoplasmosis several cerebral anomalies also have been reported, and worldwide, approximately two billion people are chronically infected with T. "gondii"…

  5. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  6. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  7. Murine Flexor Tendon Injury and Repair Surgery.

    Science.gov (United States)

    Ackerman, Jessica E; Loiselle, Alayna E

    2016-01-01

    Tendon connects skeletal muscle and bone, facilitating movement of nearly the entire body. In the hand, flexor tendons (FTs) enable flexion of the fingers and general hand function. Injuries to the FTs are common, and satisfactory healing is often impaired due to excess scar tissue and adhesions between the tendon and surrounding tissue. However, little is known about the molecular and cellular components of FT repair. To that end, a murine model of FT repair that recapitulates many aspects of healing in humans, including impaired range of motion and decreased mechanical properties, has been developed and previously described. Here an in-depth demonstration of this surgical procedure is provided, involving transection and subsequent repair of the flexor digitorum longus (FDL) tendon in the murine hind paw. This technique can be used to conduct lineage analysis of different cell types, assess the effects of gene gain or loss-of-function, and to test the efficacy of pharmacological interventions in the healing process. However, there are two primary limitations to this model: i) the FDL tendon in the mid-portion of the murine hind paw, where the transection and repair occur, is not surrounded by a synovial sheath. Therefore this model does not account for the potential contribution of the sheath to the scar formation process. ii) To protect the integrity of the repair site, the FT is released at the myotendinous junction, decreasing the mechanical forces of the tendon, likely contributing to increased scar formation. Isolation of sufficient cells from the granulation tissue of the FT during the healing process for flow cytometric analysis has proved challenging; cytology centrifugation to concentrate these cells is an alternate method used, and allows for generation of cell preparations on which immunofluorescent labeling can be performed. With this method, quantification of cells or proteins of interest during FT healing becomes possible. PMID:27684281

  8. Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy

    OpenAIRE

    Tackenberg, Björn; Jelčić, Ilijas; Baerenwaldt, Anne; Wolfgang H Oertel; Sommer, Norbert; Nimmerjahn, Falk; Lünemann, Jan D.

    2009-01-01

    The inhibitory Fc-γ receptor FcγRIIB, expressed on myeloid and B cells, has a critical role in the balance of tolerance and autoimmunity, and is required for the antiinflammatory activity of intravenous Ig (IVIG) in various murine disease models. However, the function of FcγRIIB and its regulation by IVIG in human autoimmune diseases are less well understood. Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy, and IVIG is wide...

  9. Murine erythrocytes contain high levels of lysophospholipase activity

    NARCIS (Netherlands)

    Kamp, J.A.F. op den; Roelofsen, B.; Sanderink, G.; Middelkoop, E.; Hamer, R.

    1984-01-01

    Murine erythrocytes were found to be unique in the high levels of lysophospholipase activity in the cytosol of these cells. The specific activity of the enzyme in the cytosol of the murine cells is 10-times higher than in the cytosol of rabbit erythrocytes and approximately three orders of magnitude

  10. 澄江县2000~2010年伤寒、副伤寒疫情分析%Epidemic analysis of typhoid and paratyphoid in Chengjiang County between the year of 2000 and 2010

    Institute of Scientific and Technical Information of China (English)

    李鸿坤; 王双凤; 赵青; 李虹; 马重义; 马坤林

    2012-01-01

    OBJECTIVE To learn the epidemic characteristic of typhoid and para-typhoid in Chengjiang County so as to provide efficient measurements to prevent and control typhoid and para-typhoid. METHODS Analyzed the report of infectious disease and corresponding investigated materials. RESULTS There were 2 077 people infected with typhoid and para-typhoid during the year of 2000 and 2010, and there was no death case. The prevalence rate was 120.68 per one hundred thousand showing evident seasonally. The age ranged mainly from 15—50 years accounting for 68.66% (1 426/2 077) peasants, primary and junior middle school students accounted for the majority of the patients, respectively accounting for 58.45% (1 214/2 077) and 20.70% (430/2 077), the prevalence rate was higher in plain areas than in mountain areas. Most patients didn't show typical clinic symptoms. The A type pare-typhoid was the most usual founded. CONCLUSION Measurements should be made to prevent and control the epidemic situation of typhoid and para-typhoid such as monitoring suspected and fever patients, isolating and efficiently treating patients, ensuring the drinking water safety, reinforcing public health education and enhancing the awareness of preventing illness and so on.%目的 探讨澄江县伤寒、副伤寒流行特征,制定有效的控制措施.方法 对澄江县2000~2010年伤寒疫情报告及流行病学调查资料进行分析.结果 2000~2010年澄江县共报告伤寒、副伤寒病人2077例,无死亡病例,年均发病率为120.68/10万.发病具有明显的季节性;年龄主要集中在15~50岁年龄段,占68.66%(1 426/2 077);农民和中、小学生是主要的发病人群,分别占58.45% (1214/2077)、20.70% (430/2077);坝区乡镇伤寒、副伤寒发病率高于山区乡镇;临床特征不典型;近6年该县以甲型副伤寒发病为主.结论 加强发热及疑似病例的监测,规范、隔离、治疗病人,保障饮水安全,以加强健康教育,提

  11. Chronic pain - resources

    Science.gov (United States)

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- www.theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org ...

  12. Low back pain - chronic

    Science.gov (United States)

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause ...

  13. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  14. Chronic Pelvic Pain

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  15. Employees with Chronic Pain

    Science.gov (United States)

    ... Home | Accommodation and Compliance Series: Employees with Chronic Pain By Beth Loy, Ph.D. Preface Introduction Information ... at http://AskJAN.org/soar. Information about Chronic Pain How prevalent is chronic pain? Chronic pain has ...

  16. Splenectomy normalizes hematocrit in murine polycythemia vera.

    Directory of Open Access Journals (Sweden)

    Jan-Rung Mo

    Full Text Available Splenic enlargement (splenomegaly develops in numerous disease states, although a specific pathogenic role for the spleen has rarely been described. In polycythemia vera (PV, an activating mutation in Janus kinase 2 (JAK2(V617 induces splenomegaly and an increase in hematocrit. Splenectomy is sparingly performed in patients with PV, however, due to surgical complications. Thus, the role of the spleen in the pathogenesis of human PV remains unknown. We specifically tested the role of the spleen in the pathogenesis of PV by performing either sham (SH or splenectomy (SPL surgeries in a murine model of JAK2(V617F-driven PV. Compared to SH-operated mice, which rapidly develop high hematocrits after JAK2(V617F transplantation, SPL mice completely fail to develop this phenotype. Disease burden (JAK2(V617 is equivalent in the bone marrow of SH and SPL mice, however, and both groups develop fibrosis and osteosclerosis. If SPL is performed after PV is established, hematocrit rapidly declines to normal even though myelofibrosis and osteosclerosis again develop independently in the bone marrow. In contrast, SPL only blunts hematocrit elevation in secondary, erythropoietin-induced polycythemia. We conclude that the spleen is required for an elevated hematocrit in murine, JAK2(V617F-driven PV, and propose that this phenotype of PV may require a specific interaction between mutant cells and the spleen.

  17. Murine Typhus: Clinical and epidemiological aspects

    Directory of Open Access Journals (Sweden)

    Gaspar Peniche Lara

    2012-06-01

    Full Text Available 14.00 Normal 0 21 false false false ES-CO X-NONE X-NONE Rickettsia typhi is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against R. typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of Rickettsia typhi are rats (some species belonging the Rattus Genus and fleas (Xenopsylla cheopis are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi.

  18. Benzaldehyde suppresses murine allergic asthma and rhinitis.

    Science.gov (United States)

    Jang, Tae Young; Park, Chang-Shin; Kim, Kyu-Sung; Heo, Min-Jeong; Kim, Young Hyo

    2014-10-01

    To evaluate the antiallergic effects of oral benzaldehyde in a murine model of allergic asthma and rhinitis, we divided 20 female BALB/c mice aged 8-10 weeks into nonallergic (intraperitoneally sensitized and intranasally challenged to normal saline), allergic (intraperitoneally sensitized and intranasally challenged to ovalbumin), and 200- and 400-mg/kg benzaldehyde (allergic but treated) groups. The number of nose-scratching events in 10 min, levels of total and ovalbumin-specific IgE in serum, differential counts of inflammatory cells in bronchoalveolar lavage (BAL) fluid, titers of Th2 cytokines (IL-4, IL-5, IL-13) in BAL fluid, histopathologic findings of lung and nasal tissues, and expressions of proteins involved in apoptosis (Bcl-2, Bax, caspase-3), inflammation (COX-2), antioxidation (extracellular SOD, HO-1), and hypoxia (HIF-1α, VEGF) in lung tissue were evaluated. The treated mice had significantly fewer nose-scratching events, less inflammatory cell infiltration in lung and nasal tissues, and lower HIF-1α and VEGF expressions in lung tissue than the allergic group. The number of eosinophils and neutrophils and Th2 cytokine titers in BAL fluid significantly decreased after the treatment (Pbenzaldehyde exerts antiallergic effects in murine allergic asthma and rhinitis, possibly through inhibition of HIF-1α and VEGF.

  19. Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni Expressão imunohistoquímica de receptores para estrogênio e progesterona nas fases aguda e crônica da esquistossomose mansônica experimental em camundongos

    Directory of Open Access Journals (Sweden)

    Fawzia Ahmed Habib

    2010-10-01

    Full Text Available INTRODUCTION: The responsibility of Schistosoma mansoni in female infertility is still controversial. This study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. METHODS: Twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic Schistosoma mansoni infection. Histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (ER and progesterone receptor (PR expression in the endometrium. RESULTS: No secretory phase was detected in the endometrium in acute and chronic Schistosoma infection. Hormone receptor expression (ER and PR showed statistically significant differences among the groups (pINTRODUÇÃO: A responsabilidade do Schistosoma mansoni em esterilidade feminina é ainda controversa. Este estudo é conduzido para avaliar o efeito da esquistossomose mansoni aguda e crônica no endométrio usando análise de imuno-histoquímíca da expressão de receptor hormonal uterina. MÉTODOS: Vinte e quatro camundongos fêmeas albinas suíças não grávidas foram divididas em 3 grupos (controle não-infectado, grupos agudos e crônicos infeccionados com Schistosoma mansoni. As seções histológicas de espécimes uterinos foram examinadas por microscópio leve com imagem, analisando sistema para detectar no endométrio expressões histológicas estruturais, receptor de estrogênio (ER e receptor de progesterona (PR. RESULTADOS: Nenhuma fase secretora foi detectada no endométrio com infecção aguda e crônica de Schistosoma. A expressão hormonal de receptor (ER e PR mostrou diferenças estatisticamente significantes entre grupos diferentes (p<0,05 com baixa significativa hormonal de ER com infecção crônica (comparado com controle proliferativo, controle secret

  20. Release of phytotoxins by decomposing roots of Pennisetum typhoides (Borm. f. Staff et Hubb., their effect on soil fungi and succeeding crops

    Directory of Open Access Journals (Sweden)

    R. S. Kanaujia

    2014-08-01

    Full Text Available The roots of Pennisetum typhoides decomposing in normal field conditions, in sterilized soil inoculated with 15 rhizosphere fungi and in field soil maintained at various moisture levels produced vanillic acid. 3-4-dihydroxy benzoic acid and hydroxy cinnamic acid. These acids proved toxic to the rhizosphere fungi and seeds and seedlings of certain crop plants. Out of 15 rhizosphere fungal species inoculated to the soil only 6 could induce the release of toxins, moreover, the phytotoxic substances were detected from the washing of the roots collected only on the 30th day. The moisture range which showed liberation of toxins was 20-70 per cent. The time of liberation of acids in different set s varied. These were, however, frequently liberated from washings collected from roots decomposed for 15. 30 and 45 days.

  1. OBSERVATION ON THE INCIDENCE OF NON TYPHOID SALMONELLA (SEEOTYPEHAVANA, DRUG RESISTANCE AND PATHOGENIC STRENGTH TO THE CHILDREN OF less than ONE EYAR OLD AGE IRAN (1976-1986

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    S. Mehrabian

    1988-12-01

    Full Text Available A hundred and five strains of Salmonella havana were studied from the patients of pediatric hospital of Tehran and Tabriz during 1976-86. The sources of the strains in order to their frequency were from-stool, blood, spinal, fluid, wound and urine. From the epidemiological point of view Salmonella Havana is serotype of most non-typhoid Salmonella. All of the strains had drug resistancy and most of them were resistant to many drugs. Salmonella havana had been considered in the past as a serotype of nonpathogenic agent, but this work resulted that strain has Pathogenic strength to the children of under one year old age Symptoms of diseases caused by this strain were gastroenteritis, diarrhea, Vomiting fever, Focal infection, general infection and meningitis. This strain in about 20% of the cases, particularly in the children fewer than one year old age has caused death.

  2. A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children.

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    Tinh Hien Tran

    Full Text Available BACKGROUND: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-ssaV(- ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile. OBJECTIVES: We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years. METHODS: Subjects were randomly assigned to receive either a nominal dose of 5x10(9 CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS specific serum IgA and IgG ELISA. PRINCIPAL FINDINGS: One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5% of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36% of 50 subjects in the placebo group (odds ratio (OR [95%CI] = 1.23 [0.550-2.747]; p = 0.691. Faecal shedding of S. Typhi (Ty2 aroC(-ssaV(- ZH9 was detected in 51 (51%; 95% CI, 41-61% of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change in LPS specific serum IgG (day 14 or 28 and/or 50% increase (1.5 fold change in LPS specific serum IgA (day 7 or 14 from baseline was detected in 98 (97%; 95% CI, 92-99% of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29% of 50 placebo

  3. MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG.

    Science.gov (United States)

    Garg, Rohini; Akhade, Ajay Suresh; Yadav, Jitender; Qadri, Ayub

    2015-10-01

    Vi capsular polysaccharide is currently in use as a vaccine against human typhoid caused by Salmonella Typhi. The vaccine efficacy correlates with IgG anti-Vi Abs. We have recently reported that Vi can generate inflammatory responses through activation of the TLR2/TLR1 complex. In the present study, we show that immunization with Vi produces IgM as well as IgG Abs in wild type mice. This ability is not compromised in mice deficient in T cells. However, immunization of mice lacking the TLR adaptor protein, MyD88, with Vi elicits only IgM Abs. These results suggest that MyD88-dependent pro-inflammatory ability of the Vi vaccine might be vital in generating IgG Abs with this T-independent Ag.

  4. Chronic coughing

    International Nuclear Information System (INIS)

    Chronic coughing was acknowledged to result from pathological state of the respiratory organs. Cardiac diseases could be accompanied by coughing as well. It was recommended to perform x-ray examinations, including biomedical radiography of the chest, computerized tomography, scintiscanning with 67Ga-citrate, bronchi examination in order to exclude heart disease. The complex examination permitted to detect localization and type of the changes in the lungs and mediastinum, to distinguish benign tumor from malignant one

  5. Generation of a safe Salmonella Gallinarum vaccine candidate that secretes an adjuvant protein with immunogenicity and protective efficacy against fowl typhoid.

    Science.gov (United States)

    Nandre, R M; Lee, J H

    2014-01-01

    We constructed a live, attenuated Salmonella Gallinarum (SG) that secretes heat-labile enterotoxin B subunit protein (LTB), and evaluated this strain as a new vaccine candidate by assessing its safety, immunogenicity and protective efficacy against fowl typhoid. An asd(+) p15A ori low-copy plasmid containing eltB encoding LTB was transformed into a ΔlonΔcpxRΔasd SG (JOL967) to construct the candidate, JOL1355. In Experiments 1 and 2, birds were orally immunized with JOL1355 at 4 weeks of age, while control birds were inoculated with sterile phosphate-buffered saline. In Experiment 2, the birds of both groups were orally challenged with a virulent SG at 8 weeks of age. In Experiment 1, examination for safety revealed that the immunized group did not show any bacterial counts of the vaccine candidate in the liver and spleen. Birds immunized with the vaccine candidate showed a significant increase in systemic IgG and mucosal secretory IgA levels in Experiment 2. In addition, the lymphocyte proliferation response and the numbers of CD3(+)CD4(+) and CD3(+)CD8(+) T cells were also significantly elevated in the immunized group, which indicated that the candidate also induced cellular immune responses. In the protection assay, efficient protection with only 16% mortality in the immunized group was observed against challenge compared with 76% mortality in the control group. These results indicate that the live, attenuated SG secreting LTB can be a safe vaccine candidate. In addition, it can induce humoral and cellular immune responses and can efficiently reduce mortality of birds exposed to fowl typhoid.

  6. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

    Directory of Open Access Journals (Sweden)

    Franklin R Toapanta

    2016-06-01

    Full Text Available A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD- 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h and/or microbiological (S. Typhi bacteremia endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD- was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml of TD volunteers during disease days and increase in plasmablasts (PB during the recovery phase (>day 14. Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21 and gut homing (integrin α4β7 molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

  7. Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.

    Science.gov (United States)

    Wetter, Michael; Kowarik, Michael; Steffen, Michael; Carranza, Paula; Corradin, Giampietro; Wacker, Michael

    2013-07-01

    State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization.

  8. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease

    Science.gov (United States)

    Toapanta, Franklin R.; Bernal, Paula J.; Fresnay, Stephanie; Magder, Laurence S.; Darton, Thomas C.; Jones, Claire; Waddington, Claire S.; Blohmke, Christoph J.; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.; Sztein, Marcelo B.

    2016-01-01

    A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6–9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans. PMID:27300136

  9. PCR master mixes harbour murine DNA sequences. Caveat emptor!

    Directory of Open Access Journals (Sweden)

    Philip W Tuke

    Full Text Available BACKGROUND: XMRV is the most recently described retrovirus to be found in Man, firstly in patients with prostate cancer (PC and secondly in 67% of patients with chronic fatigue syndrome (CFS and 3.7% of controls. Both disease associations remain contentious. Indeed, a recent publication has concluded that "XMRV is unlikely to be a human pathogen". Subsequently related but different polytropic MLV (pMLV sequences were also reported from the blood of 86.5% of patients with CFS. and 6.8% of controls. Consequently we decided to investigate blood donors for evidence of XMRV/pMLV. METHODOLOGY/PRINCIPAL FINDINGS: Testing of cDNA prepared from the whole blood of 80 random blood donors, generated gag PCR signals from two samples (7C and 9C. These had previously tested negative for XMRV by two other PCR based techniques. To test whether the PCR mix was the source of these sequences 88 replicates of water were amplified using Invitrogen Platinum Taq (IPT and Applied Biosystems Taq Gold LD (ABTG. Four gag sequences (2D, 3F, 7H, 12C were generated with the IPT, a further sequence (12D by ABTG re-amplification of an IPT first round product. Sequence comparisons revealed remarkable similarities between these sequences, endogeous MLVs and the pMLV sequences reported in patients with CFS. CONCLUSIONS/SIGNIFICANCE: Methodologies for the detection of viruses highly homologous to endogenous murine viruses require special caution as the very reagents used in the detection process can be a source of contamination and at a level where it is not immediately apparent. It is suggested that such contamination is likely to explain the apparent presence of pMLV in CFS.

  10. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  11. Heterohybridoma for the production of non murine monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Kh.Victoria Chanu and M. Ayub Ali

    Full Text Available Hybridoma technology described by kohler and Milstein produce only mouse immunoglobulins. Such immunoglobulins have limited use due to its negative side effects such as the recipient’s immune response. The production of a non murine monoclonal antibody to combat the problems of murine monoclonal antibody is again difficult due to the lack of a suitable myeloma cell line. Heterohybridoma formed by the fusion of lymphocyte of one species with the myeloma cell of a different species is the solution, which can be used for the production of non murine monoclonal antibodies. [Veterinary World 2010; 3(8.000: 390-392

  12. Isolation and culture of murine macrophages.

    Science.gov (United States)

    Davies, John Q; Gordon, Siamon

    2005-01-01

    The two most convenient sources of primary murine macrophages are the bone marrow and the peritoneal cavity. Resident peritoneal macrophages can readily be harvested from mice and purified by adherence to tissue culture plastic. The injection of Bio-Gel polyacrylamide beads or thioglycollate broth into the peritoneal cavity produces an inflammatory response allowing the purification of large numbers of elicited macrophages. The production of an activated macrophage population can be achieved by using Bacillus-Calmette-Guerin as the inflammatory stimulus. Resident bone marrow macrophages can be isolated following enzymatic separation of cells from bone marrow plugs and enrichment on 30% fetal calf serum containing medium or Ficoll-Hypaque gradients. Bone marrow-derived macrophages can be produced by differentiating nonadherent macrophage precursors with medium containing macrophage colony-stimulating factor.

  13. Extracellular proteolysis in the adult murine brain.

    Science.gov (United States)

    Sappino, A P; Madani, R; Huarte, J; Belin, D; Kiss, J Z; Wohlwend, A; Vassalli, J D

    1993-08-01

    Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition.

  14. Chronic Insomnia

    OpenAIRE

    Buysse, Daniel J.

    2008-01-01

    Ms. F, a 42-year-old divorced woman, presents for evaluation of chronic insomnia. She complains of difficulty falling asleep, often 30 minutes or longer, and difficulty maintaining sleep during the night, with frequent awakenings that often last 30 minutes or longer. These symptoms occur nearly every night, with only one or two “good” nights per month. She typically goes to bed around 10:00 p.m. to give herself adequate time for sleep, and she gets out of bed around 7:00 a.m. on work days and...

  15. Sensitivity of PCR assays for murine gammaretroviruses and mouse contamination in human blood samples.

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    Li Ling Lee

    Full Text Available Gammaretroviruses related to murine leukemia virus (MLV have variously been reported to be present or absent in blood from chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME patients and healthy controls. Using subjects from New York State, we have investigated by PCR methods whether MLV-related sequences can be identified in nucleic acids isolated from whole blood or from peripheral blood mononuclear cells (PBMCs or following PBMC culture. We have also passaged the prostate cancer cell line LNCaP following incubation with plasma from patients and controls and assayed nucleic acids for viral sequences. We have used 15 sets of primers that can effectively amplify conserved regions of murine endogenous and exogenous retrovirus sequences. We demonstrate that our PCR assays for MLV-related gag sequences and for mouse DNA contamination are extremely sensitive. While we have identified MLV-like gag sequences following PCR on human DNA preparations, we are unable to conclude that these sequences originated in the blood samples.

  16. Chronic Wasting Disease of Deer and Elk in Transgenic Mice: Oral Transmission and Pathobiology

    OpenAIRE

    Trifilo, Matthew J.; Ying, Ge; Teng, Chao; Oldstone, Michael B. A.

    2007-01-01

    To study the pathogenesis of chronic wasting disease (CWD) in deer and elk, transgenic (tg) mice were generated that expressed the prion protein (PrP) of deer containing a glycine at amino acid (aa) 96 and a serine at aa 225 under transcriptional control of the murine PrP promoter. This construct was introduced into murine PrP-deficient mice. As anticipated, neither non-tg mice nor PrP ko mice were susceptible when inoculated intracerebrally (i.c.) or orally with CWD brain material (scrapie p...

  17. Infection of xenotransplanted human cell lines by murine retroviruses: A lesson brought back to light by XMRV

    Directory of Open Access Journals (Sweden)

    Heidi Anne Hempel

    2013-06-01

    Full Text Available Infection of xenotransplanted human cells by xenotropic retroviruses is a known phenomenon in the scientific literature, with examples cited since the early 1970’s. However, arguably, until recently, the importance of this phenomenon had not been largely recognized. The emergence and subsequent debunking of Xenotropic Murine leukemia virus-Related Virus (XMRV as a cell culture contaminant as opposed to a potential pathogen in several human diseases, notably prostate cancer and Chronic Fatigue Syndrome, highlighted a potential problem of murine endogenous gammaretroviruses infecting commonly used human cell lines. Subsequent to the discovery of XMRV, many additional cell lines that underwent xenotransplantation in mice have been shown to harbor murine gammaretroviruses. Such retroviral infection poses the threat of not only confounding experiments performed in these cell lines via virus-induced changes in cellular behavior but also the potential infection of other cell lines cultured in the same laboratory. Thus, the possibility of xenotropic retroviral infection of cell lines may warrant additional precautions, such as periodic testing for retroviral sequences in cell lines cultured in the laboratory.

  18. Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis.

    Science.gov (United States)

    Herder, Vanessa; Iskandar, Cut Dahlia; Kegler, Kristel; Hansmann, Florian; Elmarabet, Suliman Ahmed; Khan, Muhammad Akram; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner; Beineke, Andreas

    2015-11-01

    Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.

  19. Pharmacologic inhibition of L-tyrosine degradation ameliorates cerebral dopamine deficiency in murine phenylketonuria (PKU).

    Science.gov (United States)

    Harding, Cary O; Winn, Shelley R; Gibson, K Michael; Arning, Erland; Bottiglieri, Teodoro; Grompe, Markus

    2014-09-01

    Monoamine neurotransmitter deficiency has been implicated in the etiology of neuropsychiatric symptoms associated with chronic hyperphenylalaninemia in phenylketonuria (PKU). Two proposed explanations for neurotransmitter deficiency in PKU include first, that chronically elevated blood L-phenylalanine (Phe) inhibits the transport of L-tyrosine (Tyr) and L-tryptophan (Trp), the substrates for dopamine and serotonin synthesis respectively, into brain. In the second hypothesis, elevated Phe competitively inhibits brain tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities, the rate limiting steps in dopamine and serotonin synthesis. Dietary supplementation with large neutral amino acids (LNAA) including Tyr and Trp has been recommended for individuals with chronically elevated blood Phe in an attempt to restore amino acid and monoamine homeostasis in brain. As a potential alternative treatment approach, we demonstrate that pharmacologic inhibition of Tyr degradation through oral administration of nitisinone (NTBC) yielded sustained increases in blood and brain Tyr, decreased blood and brain Phe, and consequently increased dopamine synthesis in a murine model of PKU. Our results suggest that Phe-mediated inhibition of TH activity is the likely mechanism of impaired dopamine synthesis in PKU. Pharmacologic inhibition of Tyr degradation may be a promising adjunct therapy for CNS monoamine neurotransmitter deficiency in hyperphenylalaninemic individuals with PKU. PMID:24487571

  20. Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro.

    OpenAIRE

    Ishibashi, T.; Koziol, J A; Burstein, S A

    1987-01-01

    To determine if erythropoietin affects megakaryocytopoiesis, we measured acetylcholinesterase (AchE) activity, a marker of the murine megakaryocytic lineage, after the addition of human recombinant erythropoietin to serumless murine bone marrow cultures. Erythropoietin increased AchE activity substantially. Moreover, when the hormone was added to serumless cultures of 426 isolated single megakaryocytes derived from megakaryocytic colonies, erythropoietin induced a significant increase in the ...

  1. Dynamic Determination of Oxygenation and Lung Compliance in Murine Pneumonectomy

    OpenAIRE

    Gibney, Barry; Lee, Grace S; Houdek, Jan; Lin, Miao; Miele, Lino; Chamoto, Kenji; Konerding, Moritz A; Tsuda, Akira; Mentzer, Steven J.

    2011-01-01

    Thoracic surgical procedures in mice have been applied to a wide range of investigations, but little is known about the murine physiologic response to pulmonary surgery. Using continuous arterial oximetry monitoring and the FlexiVent murine ventilator, we investigated the effect of anesthesia and pneumonectomy on mouse oxygen saturation and lung mechanics. Sedation resulted in a dose-dependent decline of oxygen saturation that ranged from 55–82%. Oxygen saturation was restored by mechanical v...

  2. Chronic kidney disease

    Science.gov (United States)

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... 2012_CKD_GL.pdf . McCullough PA. Interface between renal disease ... patients with kidney failure. N Engl J Med . 2010;362(14):1312- ...

  3. Chronic Trichuris muris infection decreases diversity of the intestinal microbiota and concomitantly increases the abundance of lactobacilli

    DEFF Research Database (Denmark)

    Holm, Jacob Bak; Sorobetea, Daniel; Kiilerich, Pia;

    2015-01-01

    microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal...

  4. A imunidade na febre tifóide I. A vacinação anti-tifoídica de Wright, 1896 a 1979 Immunity in typhoid fever. I. The anti-typhoid vaccine of Wristh, 1896 to 1979

    Directory of Open Access Journals (Sweden)

    Arlete Moreira Milhomem

    1982-03-01

    período, enquanto duas doses (intervalo de 4 semanas dão maior proteção e por tempo mais longo; g a proteção oferecida pela vacinação é maior nos jovens que nos adultos; h a vacina oral inativada (Typhoral não oferece proteção mesmo em doses elevadas. Algumas experiências com animais (camundongos, chimpanzés e voluntários humanos indicaram que uma melhor proteção foi obtida com vacinas vivas atenuadas. Contudo em tais experiências houve persistência tanto da amostra vacinante como da amostra desafio e ainda uma relação significante entre a amostra da vacina rugosa utilizada para imunização e lesões renais abacterianas de natureza desconhecida.The present comprehensive review deals with the available literature on anti-typhoid vaccines. Among the biological products, no other has raised as much controversy regarding efficacy as this commom preventive, since its early introduction by Wright, Pfeiffer & Kole. From the beginning the lack of an adequate experimental procedure for testing the vaccine potency was felt, and only poor and partial data were gathered, both from human and animal models, in relation to the basic immunological mechanism of the response to vaccination. For this reason a number of different methods have been proposed and used leading to variations in such aspects as: a the nature of bacterial strains for preparing the vaccine; b the handling of vaccine strains-killed by heat, various chemicals (alcohol, ether acetone or lysed, or employing avirulent strains; c the addition of different components (preservatives and related microrganisms; d the route of application (subcutaneous, intradermal, oral, etc; e the dose (number of organisms; f the time schedule for application. Many field trials failed to be conclusive. It is considered that the early field trials lacked proper controls, which were introduced later, in the well planned investigations sponsored by World Health Organization, in several parts of the World (Yugoslavia

  5. Atypical Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

  6. Research on Growth Behavior of Embryos for Bovine and Murine on Primary Murine Embryos Fibroblast Cell Feeder Layer

    Institute of Scientific and Technical Information of China (English)

    AN Li-long; XIAO Mei; FENG Xiu-Liang; DOU Zhong-ying; QIU Huai; YANG Qi; LEI An-min; YANG Chun-rong; GAO Zhi-min

    2002-01-01

    The difference in growth behavior between bovine embryos and murine embryos was studied on PMEF(primary murine embryos fibroblast)feeder layer. The results showed as follows: With embryos having attached, bovine embryonic trophoblast formed a transparent membranous structure covering on inner cell mass (ICM), however, murine embryonic trophoblast formed disc structure. Bovine embryos formed four kinds of ICM colonies with different morphology including the mass-like, the net-like, the stream-like and the mixture-like colonies. Compared with Murine ICM, the bovine ICM grew more fast. So, the bovine ICM was passaged at first after a culture of approximately 5 - 6 days in vitro, but murine ICM was passaged at first after an attachment of 3 - 4 days on PMEF feeder layer. The mixture colonies of bovine ICM differentiated very early, while the others differentiated very late. Most ICM-like mass of Bovine grew in a defined spot, but bovine ICMs like stream and ICMs like net proliferated fast and dispersed quickly. We found that the single blastomeres derived from late bovine morula and late murine morula formed sub-blastophere; moreover, the bovine ICM cell would differentiate rapidly if the trophoblast was removed.

  7. Influence of Pullorosis Fowl Typhoid on the Production Performance of Chicken%鸡白痢鸡伤寒对种鸡生产性能的影响

    Institute of Scientific and Technical Information of China (English)

    时倩; 潘玲; 周杰

    2011-01-01

    鸡白痢鸡伤寒是一种经蛋垂直传播且具有严重危害性的传染病.为在种鸡群中进行血清学检查,检出并淘汰阳性鸡以确保无白痢的健康种鸡群,达到种群净化的目的,本研究应用全血平板凝集试验对江苏太仓广东温氏家禽有限公司某种鸡场的5133羽新兴黄鸡进行了检测.检测结果:鸡白痢鸡伤寒的抗体阳性检出率为2.7%.在相同的饲养环境下通过为时40 d试验,对阳性鸡群与阴性鸡群的产蛋率,受精率及孵化率进行比较观察,结果表明:鸡白痢鸡伤寒抗体呈阳性鸡群的上述生产性能在不同程度上低于抗体呈阴性鸡群.鸡白痢疾鸡伤寒阳性带菌鸡群的产蛋率、受精率、孵化率分别低于鸡白痢阴性鸡群为8.1%~21.8%、0.87%~1.6%、10.6%~1 1.4%.%The Pullorosis fowl typhoid is a severe contagious disease, which spreads out perpendicularly via eggs. To eliminate the positive individuals and purify heath group, in this research we carried out serological detection in chicken. We applied the whole blood agglutination plate to assess the 5133 samples of 'Xinxinghuang' chicken in the Taicang of Guangdong Wen's Poultry Ltd. The result showed that the positive samples of the Pullorosis fowl typhoid is 2.7%. Under the same condition, we compared positive groups with negative groups in the laying rate, fertilization and hatching rate and found that production capability of positive groups was lower than the negative groups in the different degree with the ranges of 8.1-21.8% (laying rate), 0.87%-1.6% (fertilization), 10.60%-11.43% (hatching rate), respectively.

  8. Chronic mucus hypersecretion

    DEFF Research Database (Denmark)

    Harmsen, L; Thomsen, S F; Sylvan Ingebrigtsen, Truls;

    2010-01-01

    Chronic mucus hypersecretion (CMH) is a common condition in patients with chronic respiratory diseases. Little is known about the incidence, prevalence and determinants of CMH in younger individuals....

  9. Remodeling of alveolar septa after murine pneumonectomy.

    Science.gov (United States)

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  10. Isolation of Murine Embryonic Hemogenic Endothelial Cells.

    Science.gov (United States)

    Fang, Jennifer S; Gritz, Emily C; Marcelo, Kathrina L; Hirschi, Karen K

    2016-01-01

    The specification of hemogenic endothelial cells from embryonic vascular endothelium occurs during brief developmental periods within distinct tissues, and is necessary for the emergence of definitive HSPC from the murine extra embryonic yolk sac, placenta, umbilical vessels, and the embryonic aorta-gonad-mesonephros (AGM) region. The transient nature and small size of this cell population renders its reproducible isolation for careful quantification and experimental applications technically difficult. We have established a fluorescence-activated cell sorting (FACS)-based protocol for simultaneous isolation of hemogenic endothelial cells and HSPC during their peak generation times in the yolk sac and AGM. We demonstrate methods for dissection of yolk sac and AGM tissues from mouse embryos, and we present optimized tissue digestion and antibody conjugation conditions for maximal cell survival prior to identification and retrieval via FACS. Representative FACS analysis plots are shown that identify the hemogenic endothelial cell and HSPC phenotypes, and describe a methylcellulose-based assay for evaluating their blood forming potential on a clonal level. PMID:27341393

  11. Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.

    Directory of Open Access Journals (Sweden)

    Laurent Gillet

    Full Text Available Glycosaminoglycans (GAGs commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68 infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces.

  12. Amphotropic murine leukemia viruses induce spongiform encephalomyelopathy.

    Science.gov (United States)

    Münk, C; Löhler, J; Prassolov, V; Just, U; Stockschläder, M; Stocking, C

    1997-05-27

    Recombinants of amphotropic murine leukemia virus (A-MuLV) have found widespread use in retroviral vector systems due to their ability to efficiently and stably infect cells of several different species, including human. Previous work has shown that replication-competent recombinants containing the amphotropic env gene, encoding the major SU envelope glycoprotein that determines host tropism, induce lymphomas in vivo. We show here that these viruses also induce a spongiform encephalomyelopathy in mice inoculated perinatally. This fatal central nervous system disease is characterized by noninflammatory spongiform lesions of nerve and glial cells and their processes, and is associated with moderate astro- and microgliosis. The first clinical symptoms are ataxia, tremor, and spasticity, progressing to complete tetraparesis and incontinence, and finally death of the animal. Sequences within the amphotropic env gene are necessary for disease induction. Coinfection of A-MuLV recombinants with nonneuropathogenic ecotropic or polytropic MuLV drastically increases the incidence, degree, and distribution of the neurodegenerative disorder. The consequence of these results in view of the use of A-MuLV recombinants in the clinic is discussed.

  13. Chronic urticaria

    Directory of Open Access Journals (Sweden)

    Sandeep Sachdeva

    2011-01-01

    Full Text Available Chronic urticaria (CU is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the ′idiopathic′ forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.

  14. Local immunotherapy in experimental murine lung inflammation

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Caroline Uebel, Sonja Koch, Anja Maier, Nina Sopel, Anna Graser, Stephanie Mousset & Susetta Finotto ### Abstract Innovative local immunotherapy for severe lung diseases such as asthma, chronic obstructive pulmonary disease or lung cancer requires a successful delivery to access the desired cellular target in the lung. An important route is the direct instillation into the airways in contrast to delivery through the digestive tract. This protocol details a method to deliv...

  15. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M;

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...

  16. Chronic Rhinosinusitis and the Coagulation System.

    Science.gov (United States)

    Kim, Dong Young; Cho, Seong H; Takabayashi, Tetsuji; Schleimer, Robert P

    2015-09-01

    Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in adults and severely affects quality of life in patients. Although various etiologic and pathogenic mechanisms of CRS have been proposed, the causes of CRS remain uncertain. Abnormalities in the coagulation cascade may play an etiologic role in many diseases, such as asthma and other inflammatory conditions. While studies on the relationship between asthma and dysregulated coagulation have been reported, the role of the coagulation system in the pathogenesis of CRS has only been considered following recent reports. Excessive fibrin deposition is seen in nasal polyp (NP) tissue from patients with chronic rhinosinusitis with nasal polyp (CRSwNP) and is associated with activation of thrombin, reduction of tissue plasminogen activator (t-PA) and upregulation of coagulation factor XIII-A (FXIII-A), all events that can contribute to fibrin deposition and crosslinking. These findings were reproduced in a murine model of NP that was recently established. Elucidation of the mechanisms of fibrin deposition may enhance our understanding of tissue remodeling in the pathophysiology of NP and provide new targets for the treatment of CRSwNP. PMID:26122502

  17. Oral infection with the Salmonella enterica serovar Gallinarum 9R attenuated live vaccine as a model to characterise immunity to fowl typhoid in the chicken

    Directory of Open Access Journals (Sweden)

    Beal Richard

    2005-09-01

    Full Text Available Abstract Background Salmonella enterica serovar Gallinarum (S. Gallinarum is the causative agent of fowl typhoid, a severe systemic disease of chickens that results in high mortality amongst infected flocks. Due to its virulence, the immune response to S. Gallinarum is poorly characterised. In this study we have utilised infection by the live attenuated S. Gallinarum 9R vaccine strain in inbred chickens to characterise humoral, cellular and cytokine responses to systemic salmonellosis. Results Infection with 9R results in a mild systemic infection. Bacterial clearance at three weeks post infection coincides with increases in circulating anti-Salmonella antibodies, increased T cell proliferation to Salmonella challenge and increased expression of interferon gamma. These responses peak at four weeks post infection, then decline. Only modest increases of expression of the pro-inflammatory cytokine interleukin-1β were detected early in the infection. Conclusion Infection of chickens with the 9R vaccine strain induces a mild form of systemic salmonellosis. This induces both cellular and humoral immune responses, which peak soon after bacterial clearance. Unlike enteric-associated Salmonella infections the immune response is not prolonged, reflecting the absence of persistence of Salmonella in the gastrointestinal tract. The findings here indicate that the use of the S. Gallinarum 9R vaccine strain is an effective model to study immunity to systemic salmonellosis in the chicken and may be employed in further studies to determine which components of the immune response are needed for protection.

  18. The antibiotic resistance characteristics of non-typhoidal Salmonella enterica isolated from food-producing animals, retail meat and humans in South East Asia.

    Science.gov (United States)

    Van, Thi Thu Hao; Nguyen, Hoang Nam Kha; Smooker, Peter M; Coloe, Peter J

    2012-03-15

    Antimicrobial resistance is a global problem. It is most prevalent in developing countries where infectious diseases remain common, the use of antibiotics in humans and animals is widespread, and the replacement of older antibiotics with new generation antibiotics is not easy due to the high cost. Information on antibiotic resistance phenotypes and genotypes of Salmonella spp. in food animals and humans in different countries and geographic regions is necessary to combat the spread of resistance. This will improve the understanding of antibiotic resistance epidemiology, tracing of new emerging pathogens, assisting in disease treatment, and enhancing prudent use of antibiotics. However, the extent of antibiotic resistance in food-borne pathogens and humans in many developing countries remains unknown. The goal of this review is to discuss the current state of antibiotic resistance of non-typhoid Salmonella spp. in food-producing animals, retail meat and humans from South East Asia. It is focused on resistance characteristics of traditional and "critically important" antibiotics in this region, and the emergence of multidrug resistant strains and genetic elements that contribute to the development of multidrug resistance, including integrons and the Salmonella Genomic Island (SGI).

  19. Role of gum chewing on the duration of postoperative ileus following ileostomy closure done for typhoid ileal perforation: A prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Sanjay Marwah

    2012-01-01

    Full Text Available Background/Aim : There is ample evidence in the recent literature that gum chewing after elective colonic anastomosis decreases postoperative ileus (POI. But there are very few studies on small bowel anastomosis done in relaparotomy cases. This study aimed to evaluate the effect of gum chewing on the duration of POI following small bowel anastomosis performed for the closure of intestinal stoma, made as temporary diversion in the selected cases of typhoid perforation peritonitis. Patients and Methods : Hundred patients undergoing elective small bowel anastomosis for the closure of stoma were randomly assigned to the study group (n=50 and the control group (n=50. The study group patients chewed gum thrice a day for 1 h each time starting 6 h after the surgery until the passage of first flatus. The control group patients had standard postoperative treatment. Results : Study and control group patients were comparable at inclusion. The mean time for the appearance of bowel sounds as well as the passage of first flatus was significantly shorter in the study group (P=0.040, P=0.006. The feeling of hunger was also experienced earlier in study group cases (P=0.004. The postoperative hospital stay was shorter in the study group, but the difference was not significant (P=0.059. Conclusions: The cases of relaparotomy requiring additional adhesiolysis and small bowel anastomosis for stoma closure are benefited by postoperative gum chewing.

  20. Safety and protective efficacy of a spiC and crp deletion mutant of Salmonella gallinarum as a live attenuated vaccine for fowl typhoid.

    Science.gov (United States)

    Cheng, Zhao; Yin, Junlei; Kang, Xilong; Geng, Shizhong; Hu, Maozhi; Pan, Zhiming; Jiao, Xinan

    2016-08-01

    With an aim to develop a safe, immunogenic fowl typhoid (FT) vaccine, the safety and efficacy of 1009ΔspiCΔcrp, a spiC and crp deletion mutant of Salmonella gallinarum, were evaluated in chickens. Three-day-old chickens were intramuscularly immunized with 1009ΔspiCΔcrp (1×10(7)CFU) and boosted 7days later (at 10-days old) with the same dose and via the same route (vaccinated group). The vaccinated group showed no clinical symptoms and no differences in body weight compared to the unvaccinated control group. 1009ΔspiCΔcrp bacteria colonized and persisted in the liver and spleen of vaccinated chickens for >14days, and significant specific humoral and cellular immune responses were induced. Vaccinated chickens were challenged with S. gallinarum strain SG9 at 21days post-immunization (24-day-old chickens), and efficient protection was observed based on the mortality and clinical symptoms, as compared to those in the control group. These results demonstrate that 1009ΔspiCΔcrp can be used as a live attenuated vaccine. PMID:27473974

  1. Antimicrobial resistance in invasive non-typhoid Salmonella from the Democratic Republic of the Congo: emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases.

    Directory of Open Access Journals (Sweden)

    Octavie Lunguya

    Full Text Available BACKGROUND: Co-resistance against the first-line antibiotics ampicillin, chloramphenicol and trimethoprim/sulphamethoxazole or multidrug resistance (MDR is common in non typhoid Salmonella (NTS. Use of alternative antibiotics, such as fluoroquinolones or third generation cephalosporins is threatened by increasing resistance, but remains poorly documented in Central-Africa. METHODOLOGY/PRINCIPAL FINDINGS: As part of a microbiological surveillance study in DR Congo, blood cultures were collected between 2007 and 2011. Isolated NTS were assessed for serotype and antimicrobial resistance including decreased ciprofloxacin susceptibility and extended-spectrum beta-lactamase (ESBL production. In total, 233 NTS isolates (representing 23.6% of clinically significant organisms were collected, mainly consisting of Salmonella Typhimurium (79% and Salmonella Enteritidis (18%. The majority of NTS were isolated in the rainy season, and recovered from children ≤2 years old. MDR, decreased ciprofloxacin susceptibility, azithromycin and cefotaxime resistance were 80.7%, 4.3%, 3.0% and 2.1% respectively. ESBL production was noted in three (1.3% isolates. Decreased ciprofloxacin susceptibility was associated with mutations in codon 87 of the gyrA gene, while ESBLs all belonged to the SHV-2a type. CONCLUSIONS/SIGNIFICANCE: Presence of almost full MDR among NTS isolates from blood cultures in Central Africa was confirmed. Resistance to fluoroquinolones, azithromycin and third generation cephalosporins is still low, but emerging. Increased microbiological surveillance in DR Congo is crucial for adapted antibiotic therapy and the development of treatment guidelines.

  2. Analysis of cardiomyocyte movement in the developing murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  3. Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

    Directory of Open Access Journals (Sweden)

    Gurjot Basra

    2012-01-01

    Full Text Available Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient’s acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.

  4. Analysis of cardiomyocyte movement in the developing murine heart

    International Nuclear Information System (INIS)

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development

  5. Isotype specific immune responses in murine experimental toxocariasis

    Directory of Open Access Journals (Sweden)

    Cuéllar C

    2001-01-01

    Full Text Available In this work, a murine experimental model of toxocariasis has been developed in BALB/c, C57BL/10 and C3H murine strains orally inoculated with 4,000 Toxocara canis embryonated eggs, in order to investigate the isotype-specific immune responses against excretory-secretory antigens from larvae. T. canis specific IgG+M, IgM, IgG, IgA, IgG1, IgG2a and IgG3 were tested by ELISA. The dynamics of the specific immunoglobulins (IgG+IgM production showed a contrasting profile regarding the murine strain. Conversely to the results obtained with the IgM isotype, the IgG antibody class showed similar patterns to those obtained with IgG+IgM antibodies, only in the case of the BALB/c strain, being different and much higher than the obtained with IgG+IgM antibodies, when the C3H murine strain was used. The antibodies IgG+IgM tested in BALB/c and C57BL/10 were both of the IgM and IgG isotypes. Conversely, in the C3H strain only IgG specific antibody levels were detected. The IgG1 subclass responses showed a similar profile in the three murine strains studied, with high values in BALB/c, as in the case of the IgG responses.

  6. Apoptosis and the thymic microenvironment in murine lupus.

    Science.gov (United States)

    Takeoka, Y; Taguchi, N; Shultz, L; Boyd, R L; Naiki, M; Ansari, A A; Gershwin, M E

    1999-11-01

    The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.

  7. Neuromodulation of chronic headaches

    DEFF Research Database (Denmark)

    Martelletti, Paolo; Jensen, Rigmor H; Antal, Andrea;

    2013-01-01

    The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even...

  8. Experimental murine chromoblastomycosis obtained from Fonsecaea pedrosoi isolate cultured for a long periodt

    Directory of Open Access Journals (Sweden)

    AP Machado

    2009-01-01

    Full Text Available The present study aimed to describe F. pedrosoi propagules capable of causing chronic murine disease. Several changes in F. pedrosoi hyphae were identified in fungal cells cultured for a long period. Optical microscopy found many rounded cells with double-rigid melanin-rich walls. Terminal and intercalary chlamydoconidia were also frequently observed. Analyses of images from transmission electron microscopy (TEM revealed several cells with walls composed of at least three layers and an outer layer enriched with melanin. Two groups of twenty BALB/c mice were subcutaneously infected in their footpads with F. pedrosoi cells at an inoculum concentration of approximately 1 x 10(4 cells/mL. In one group, long-term cultured F. pedrosoi cells were inoculated in one footpad, whereas in the other group, both footpads were infected. Active lesions were observed up to seven months post-infection, particularly in mice inoculated at two sites. After this period, animals were killed. Histological sections revealed characteristics bearing a strong resemblance to the human form of the disease such as tissue hyperplasia, granulomas with microabscesses and sclerotic cells. Based on this study, we identified fungal cells from old cultures capable of provoking chronic chromoblastomycosis under experimental conditions, especially when more than one site is infected.

  9. Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation from Latency by Preventing Virus-Induced Systemic Inflammation.

    Science.gov (United States)

    Park, Sunmin; Buck, Michael D; Desai, Chandni; Zhang, Xin; Loginicheva, Ekaterina; Martinez, Jennifer; Freeman, Michael L; Saitoh, Tatsuya; Akira, Shizuo; Guan, Jun-Lin; He, You-Wen; Blackman, Marcia A; Handley, Scott A; Levine, Beth; Green, Douglas R; Reese, Tiffany A; Artyomov, Maxim N; Virgin, Herbert W

    2016-01-13

    Host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. Murine gammaherpesvirus 68 (MHV68) infection is characterized by latency in macrophages, and reactivation is inhibited by interferon-γ (IFN-γ). Using a lysozyme-M-cre (LysMcre) expression system, we show that deletion of autophagy-related (Atg) genes Fip200, beclin 1, Atg14, Atg16l1, Atg7, Atg3, and Atg5, in the myeloid compartment, inhibited MHV68 reactivation in macrophages. Atg5 deficiency did not alter reactivation from B cells, and effects on reactivation from macrophages were not explained by alterations in productive viral replication or the establishment of latency. Rather, chronic MHV68 infection triggered increased systemic inflammation, increased T cell production of IFN-γ, and an IFN-γ-induced transcriptional signature in macrophages from Atg gene-deficient mice. The Atg5-related reactivation defect was partially reversed by neutralization of IFN-γ. Thus Atg genes in myeloid cells dampen virus-induced systemic inflammation, creating an environment that fosters efficient MHV68 reactivation from latency. PMID:26764599

  10. OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature

    Directory of Open Access Journals (Sweden)

    Nicolle Jasmin Domnik

    2012-12-01

    Full Text Available Altered autonomic (ANS tone in chronic respiratory disease is implicated as a factor in cardiovascular co-morbidities, yet no studies address its impact on cardiovascular function in the presence of murine allergic airway (AW hyperresponsiveness (AHR. Since antigen (Ag-induced AHR is used to model allergic asthma (in which ANS alterations have been reported, we performed a pilot study to assess measurement feasibility of, as well as the impact of allergic sensitization to ovalbumin (OVA on, heart rate variability (HRV in a murine model. Heart rate (HR, body temperature (TB and time- and frequency-domain HRV analyses, a reflection of ANS control, were obtained in chronically instrumented mice (telemetry before, during and for 22 h after OVA or saline aerosolization in sensitized (OVA or Alum adjuvant control exposed animals. OVA mice diverged significantly from Alum mice with respect to change in HR during aerosol challenge (P < 0.001, two-way ANOVA; HR max change Ctrl = +80 ± 10 bpm vs. OVA = +1 ± 23 bpm, mean ± SEM, and displayed elevated HR during the subsequent dark cycle (P = 0.006. Sensitization decreased the TB during aerosol challenge (P < 0.001. Sensitized mice had decreased HRV prior to challenge (SDNN: P = 0.038; Low frequency (LF power: P = 0.021; Low/high Frequency (HF power: P = 0.042, and increased HRV during Ag challenge (RMSSD: P = 0.047; pNN6: P = 0.039. Sensitized mice displayed decreased HRV subsequent to OVA challenge, primarily in the dark cycle (RMSSD: P = 0.018; pNN6: P < 0.001; LF: P < 0.001; HF: P = 0.040; LF/HF: P < 0.001. We conclude that implanted telemetry technology is an effective method to assess the ANS impact of allergic sensitization. Preliminary results show mild sensitization is associated with reduced HRV and a suppression of the acute TB response to OVA challenge. This approach to assess altered ANS control in the acute OVA model may also be beneficial in chronic AHR models.

  11. Untying chronic pain

    OpenAIRE

    Häuser, Winfried; Wolfe, Frederik; Henningsen, Peter; Schmutzer, Gabriele; Brähler, Elmar; Hinz, Andreas

    2014-01-01

    Background: Chronic pain is a major public health problem. The impact of stages of chronic pain adjusted for disease load on societal burden has not been assessed in population surveys. Methods: A cross-sectional survey with 4360 people aged ≥ 14 years representative of the German population was conducted. Measures obtained included demographic variables, presence of chronic pain (based on the definition of the International Association for the Study of Pain), chronic pain stages (by chronic ...

  12. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  13. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B; Nikolajsen, L; Kehlet, Henrik;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies. Udgivelsesdato: 2008-Mar...

  14. Effect of Hedera helix on lung histopathology in chronic asthma.

    OpenAIRE

    Arzu Babayigit Hocaoglu; Ozkan Karaman; Duygu Olmez Erge; Guven Erbil; Osman Yilmaz; Bijen Kivcak; H Alper Bagriyanik; Nevin Uzuner

    2012-01-01

    Hedera helix  is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c  mice  were  divided  into  four  groups;   I  (Placebo),  II  (Hedera  helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group ...

  15. Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease

    OpenAIRE

    Fransolet, Gilles; Ehx, Grégory; Somja, Joan; Delens, Loïc; Hannon, Muriel; Muller, Joséphine; Dubois, Sophie; Drion, Pierre; Caers, Jo; Humblet-Baron, Stéphanie; Delvenne, Philippe; Beguin, Yves; Conteduca, Giuseppina; Baron, Frédéric

    2016-01-01

    Background Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4+ T cells (CD4+Tconvs) but demethylated in Tregs. Methods Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) → BALB/cJ ...

  16. Isoforms of murine and human serum amyloid P component

    DEFF Research Database (Denmark)

    Nybo, Mads; Hackler, R; Kold, B;

    1998-01-01

    Isoelectric focusing (IEF) and immunofixation of murine serum amyloid P component (SAP), purified and in serum, showed a distinct and strain-dependent isoform pattern with up to seven bands (pI 5.1-5.7). Neuraminidase treatment caused a shift of the isoforms to more basic pI values, but did...... of isoforms of human SAP required the presence of urea and higher SAP concentrations. TEF and immunofixation of SAP monomers showed five to eight isoforms, ranging from pI 4.7-5.7. IEF of SAP in human serum resulted in a less distinct pattern and more acidic isoforms. As with murine SAP, neuraminidase...

  17. A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Ryan W Carroll

    Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

  18. Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

    Science.gov (United States)

    Jones, Claire; Blohmke, Christoph J.; Waddington, Claire S.; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A.; Jeppesen, Catherine A.; Moore, Maria; Thompson, Ben A. V.; John, Tessa; Kingsley, Robert A.; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.

    2016-01-01

    Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge

  19. Nanoelectroablation therapy for murine basal cell carcinoma

    International Nuclear Information System (INIS)

    Highlights: ► Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. ► Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. ► Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. ► Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1+/−K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5–7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 ± 5 (SEM) mm3 shrunk by 76 ± 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  20. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  1. Fitness of isogenic colony morphology variants of Pseudomonas aeruginosa in murine airway infection.

    Directory of Open Access Journals (Sweden)

    Elza Rakhimova

    Full Text Available Chronic lung infections with Pseudomonas aeruginosa are associated with the diversification of the persisting clone into niche specialists and morphotypes, a phenomenon called 'dissociative behaviour'. To explore the potential of P. aeruginosa to change its morphotype by single step loss-of-function mutagenesis, a signature-tagged mini-Tn5 plasposon library of the cystic fibrosis airway isolate TBCF10839 was screened for colony morphology variants under nine different conditions in vitro. Transposon insertion into 1% of the genome changed colony morphology into eight discernable morphotypes. Half of the 55 targets encode features of primary or secondary metabolism whereby quinolone production was frequently affected. In the other half the transposon had inserted into genes of the functional categories transport, regulation or motility/chemotaxis. To mimic dissociative behaviour of isogenic strains in lungs, pools of 25 colony morphology variants were tested for competitive fitness in an acute murine airway infection model. Six of the 55 mutants either grew better or worse in vivo than in vitro, respectively. Metabolic proficiency of the colony morphology variant was a key determinant for survival in murine airways. The most common morphotype of self-destructive autolysis did unexpectedly not impair fitness. Transposon insertions into homologous genes of strain PAO1 did not reproduce the TBCF10839 mutant morphotypes for 16 of 19 examined loci pointing to an important role of the genetic background on colony morphology. Depending on the chosen P. aeruginosa strain, functional genome scans will explore other areas of the evolutionary landscape. Based on our discordant findings of mutant phenotypes in P. aeruginosa strains PAO1, PA14 and TBCF10839, we conclude that the current focus on few reference strains may miss modes of niche adaptation and dissociative behaviour that are relevant for the microevolution of complex traits in the wild.

  2. In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosomiasis [corrected].

    Directory of Open Access Journals (Sweden)

    Brice Masi

    2015-09-01

    Full Text Available Schistosomiasis (or bilharzia, a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI and evaluated the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis.CBA/J mice were imaged at 11.75 T two, six and ten weeks after percutaneous infection with Schistosoma mansoni. In vivo imaging studies were completed with histology at the last two time points. Anatomical MRI allowed detection of typical manifestations of the intestinal disease such as significant hepato- and splenomegaly, and dilation of the portal vein as early as six weeks, with further aggravation at 10 weeks after infection. Liver multifocal lesions observed by MRI in infected animals at 10 weeks post infection corresponded to granulomatous inflammation and intergranulomatous fibrosis with METAVIR scores up to A2F2. While most healthy hepatic tissue showed T2 values below 14 ms, these lesions were characterized by a T2 greater than 16 ms. The area fraction of increased T2 correlated (rS = 0.83 with the area fraction of Sirius Red stained collagen in histological sections. A continuous liver T2* decrease was also measured while brown pigments in macrophages were detected at histology. These findings suggest accumulation of hematin in infected livers.Our multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T2 mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment

  3. Degeneration in Arousal Neurons in Chronic Sleep Disruption Modeling Sleep Apnea

    OpenAIRE

    Zhu, Yan; Fenik, Polina; Zhan, Guanxia; Xin, Ryan; Veasey, Sigrid C.

    2015-01-01

    Chronic sleep disruption (CSD) is a cardinal feature of sleep apnea that predicts impaired wakefulness. Despite effective treatment of apneas and sleep disruption, patients with sleep apnea may have persistent somnolence. Lasting wake disturbances in treated sleep apnea raise the possibility that CSD may induce sufficient degeneration in wake-activated neurons (WAN) to cause irreversible wake impairments. Implementing a stereological approach in a murine model of CSD, we found reduced neurona...

  4. A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

    Directory of Open Access Journals (Sweden)

    Yang Hong-hui

    2005-05-01

    Full Text Available Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90% than in adolescents and young adults (70%. Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%, malaise (19% and local redness (19% were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

  5. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  6. Increased rejection of murine allogeneic bone marrow in presensitized recipients

    NARCIS (Netherlands)

    vanOs, R; deWitte, T; Dillingh, JH; Mauch, PM; Down, JD

    1997-01-01

    The role of presensitizing murine recipients with donor spleen cells prior to T cell-depleted or -repleted H-2 compatible allogeneic bone marrow transplantation (BMT) was investigated at two different doses of total body irradiation (TBI). Recipients that were presensitized with 2 x 10(7) irradiated

  7. Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin

    Institute of Scientific and Technical Information of China (English)

    Guang-Hong Tan; Feng-Ying Huang; Hua Wang; Yong-Hao Huang; Ying-Ying Lin; Yue-Nan Li

    2007-01-01

    AIM: To explore the capability of a monoclonal antibody(mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models.METHODS: A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay.RESULTS: Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice.Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with antiendoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb.CONCLUSION: Passive immunotherapy with antiendoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.

  8. Pharmacodynamics of Doxycycline in a Murine Malaria Model▿

    OpenAIRE

    Batty, Kevin T.; Law, Angela S. F.; Stirling, Verity; Moore, Brioni R.

    2007-01-01

    Doxycycline is reported to impair second-generation parasite schizogony. The effects of doxycycline alone and combined with dihydroartemisinin were investigated in a murine malaria model. Doxycycline lowered the rate of parasite growth within 2 days, with maximum effect in 6 days. Addition of dihydroartemisinin led to an additive antimalarial effect.

  9. Turnover of T cells in murine gammaherpesvirus 68-infected mice

    DEFF Research Database (Denmark)

    Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

  10. Murine myocardium OCT imaging with a blood substitute

    Science.gov (United States)

    Kim, Jeehyun; Villard, Joseph W.; Lee, Ho; Feldman, Marc D.; Milner, Thomas E.

    2002-06-01

    Imaging of the in vivo murine myocardium using optical coherence tomography (OCT) is described. Application of conventional techniques (e.g. MRI, Ultrasound imaging) for imaging the murine myocardium is problematic because the wall thickness is less than 1.5mm (20g mouse), and the heart rate can be as high as six-hundred beats per minute. To acquire a real-time image of the murine myocardium, OCT can provide sufficient spatial resolution (10 micrometers ) and imaging speed (1000 A-Scans/s). Strong light scattering by blood in the heart causes significant light attenuation making delineation of the endocardium-chamber boundary problematic. By replacing whole blood in the mouse with an artificial blood substitute we demonstrate significant reduction of light scattering in the murine myocardium. The results indicate a significant reduction in light scattering as whole blood hematocrit is diminished below 5%. To measure thickness change of the myocardium during one cycle, a myocardium edge detection algorithm is developed and demonstrated.

  11. Attenuated Salmonella Gallinarum secreting an Escherichia coli heat-labile enterotoxin B subunit protein as an adjuvant for oral vaccination against fowl typhoid.

    Science.gov (United States)

    Jeon, Byung Woo; Jawale, Chetan V; Kim, Seung Hwan; Lee, John Hwa

    2012-12-15

    In our previous study, we constructed a vaccine candidate (JOL916) for fowl typhoid (FT). A live adjuvant Salmonella Gallinarum (SG) strain was generated in the present study to facilitate efficacious oral vaccination with this vaccine. The Escherichia coli eltB gene secreting heat-labile enterotoxin B subunit (LTB) was cloned into an Asd(+) plasmid pJHL65. This was transformed into a Δlon ΔcpxR Δasd SG strain and the resulting strain was designated JOL1229. Secretion of LTB from JOL1229 was confirmed with an immunoblot assay. To determine the optimal dose of the strain, 50 six-week-old female chickens were divided into five groups (Groups A-E, n=10 per group) and orally inoculated with various doses of JOL1229 and JOL916. In Group B (consisting of four parts JOL916 and one part JOL1229), significant cell-mediated immune responses, plasma IgG levels and intestinal secretary IgA levels were induced after inoculation with both strains. On challenge with the wild-type strain, significant reductions in mortality were observed in the group. In addition, after inoculation the LTB strain was not recovered in feces samples, and resulted in no, or very mild, gross lesions in the liver and spleen. Both CD4(+) and CD8(+) T-cells were significantly increased in peripheral blood samples from the chickens immunized with the LTB strain. Expression of the interleukin-6 (IL-6) gene in splenocytes was induced in the chickens immunized with the LTB strain. These results suggest that oral immunization with the LTB-adjuvant strain, in particular with the four parts JOL916 and one part JOL1229 mixture, increased the immune response and provided efficient protection against FT in chickens.

  12. Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam.

    Science.gov (United States)

    Phu Huong Lan, Nguyen; Le Thi Phuong, Tu; Nguyen Huu, Hien; Thuy, Le; Mather, Alison E; Park, Se Eun; Marks, Florian; Thwaites, Guy E; Van Vinh Chau, Nguyen; Thompson, Corinne N; Baker, Stephen

    2016-08-01

    Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men. PMID:27513951

  13. Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam

    Science.gov (United States)

    Phu Huong Lan, Nguyen; Le Thi Phuong, Tu; Nguyen Huu, Hien; Thuy, Le; Mather, Alison E.; Park, Se Eun; Marks, Florian; Thwaites, Guy E.; Van Vinh Chau, Nguyen; Thompson, Corinne N.; Baker, Stephen

    2016-01-01

    Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men. PMID:27513951

  14. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine. PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. CONCLUSIONS: Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.

  15. Induction of Antimicrobial Resistance in Escherichia coli and Non-Typhoidal Salmonella Strains after Adaptation to Disinfectant Commonly Used on Farms in Vietnam

    Directory of Open Access Journals (Sweden)

    Nguyen T. Nhung

    2015-10-01

    Full Text Available In Vietnam, commercial disinfectants containing quaternary ammonium compounds (QACs are commonly used in pig and poultry farms to maintain hygiene during production. We hypothesized that sustained exposure to sub-bactericidal concentrations of QAC-based disinfectants may result in increased levels of antimicrobial resistance (AMR among Enterobacteriacea due to the increase of efflux pump expression. To test this hypothesis we exposed six antimicrobial-susceptible Escherichia coli (E. coli and six antimicrobial-susceptible non-typhoidal Salmonella (NTS isolates to increasing concentrations of a commonly used commercial disinfectant containing a mix of benzalkonium chloride and glutaraldehyde. Over the 12-day experiment, strains exhibited a significant change in their minimum inhibitory concentration (MIC of the disinfectant product (mean increase of 31% (SD ± 40 (p = 0.02, paired Wilcoxon test. Increases in MIC for the disinfectant product were strongly correlated with increases in MIC (or decreases in inhibition zone for all antimicrobials (Pearson’s correlation coefficient 0.71–0.83, all p < 0.01. The greatest increases in MIC (or decreases in inhibition zone were observed for ampicillin, tetracycline, ciprofloxacin, and chloramphenicol, and the smallest for gentamicin, trimethoprim/sulphamethoxazole. The treatment of 155 representative E. coli isolates from farmed and wild animals in the Mekong Delta (Vietnam with phenyl-arginine beta-naphthylamide (PAβN, a generic efflux pump inhibitor, resulted in reductions in the prevalence of AMR ranging from 0.7% to 3.3% in these organisms, indicating a small contribution of efflux pumps on the observed prevalence of AMR on farms. These results suggest that the mass usage of commercial disinfectants, many of which contain QACs, is potentially a contributing factor on the generation and maintenance of AMR in animal production in Vietnam.

  16. Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine candidate and its protective efficacy against fowl typhoid in chickens

    Directory of Open Access Journals (Sweden)

    Chaudhari Atul A

    2012-05-01

    Full Text Available Abstract In order to develop a novel, safe and immunogenic fowl typhoid (FT vaccine candidate, a Salmonella Gallinarum ghost with controlled expression of the bacteriophage PhiX174 lysis gene E was constructed using pMMP99 plasmid in this study. The formation of the Salmonella Gallinarum ghost with tunnel formation and loss of cytoplasmic contents was observed by scanning electron microscopy and transmission electron microscopy. No viable cells were detectable 24 h after the induction of gene E expression by an increase in temperature from 37 °C to 42 °C. The safety and protective efficacy of the Salmonella Gallinarum ghost vaccine was tested in chickens that were divided into four groups: group A (non-immunized control, group B (orally immunized, group C (subcutaneously immunized and group D (intramuscularly immunized. The birds were immunized at day 7 of age. None of the immunized animals showed any adverse reactions such as abnormal behavior, mortality, or signs of FT such as anorexia, depression, or diarrhea. These birds were subsequently challenged with a virulent Salmonella Gallinarum strain at 3 weeks post-immunization (wpi. Significant protection against the virulent challenge was observed in all immunized groups based on mortality and post-mortem lesions compared to the non-immunized control group. In addition, immunization with the Salmonella Gallinarum ghosts induced significantly high systemic IgG response in all immunized groups. Among the groups, orally-vaccinated group B showed significantly higher levels of secreted IgA. A potent antigen-specific lymphocyte activation response along with significantly increased percentages of CD4+ and CD8+ T lymphocytes found in all immunized groups clearly indicate the induction of cellular immune responses. Overall, these findings suggest that the newly constructed Salmonella Gallinarum ghost appears to be a safe, highly immunogenic, and efficient non-living bacterial vaccine

  17. Molecular analysis of ciprofloxacin resistance among non-typhoidal Salmonella with reduced susceptibility to ciprofloxacin isolated from patients at a tertiary care hospital in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Karunakaran, Rina; Tay, Sun Tee; Rahim, Fairuz Fadzilah; Lim, Bee Bee; Puthucheary, Savithri D

    2014-01-01

    We investigated the prevalence of non-typhoidal Salmonella (NTS) with "reduced susceptibility to ciprofloxacin" (RS-Cip) (minimum inhibitory concentration [MIC], 0.12-1.0 μg/mL) as well as their resistance genes in 75 NTS isolates (53 from stool, 21 from blood, and 1 from urine) from patients at a tertiary care Malaysian hospital between January and December 2009. RS-Cip was detected in 24/75 (32.0%) isolates. Using the ciprofloxacin MIC interpretive criteria for Salmonella in the Clinical and Laboratory Standards Institute 2013 guidelines, 51/75 (68.0%) isolates were found to be sensitive, 22/75 (29.3%) were intermediate, and 2/75 (2.7%) were resistant to ciprofloxacin. The 24 isolates that were intermediate or resistant to ciprofloxacin were the same isolates categorized as having RS-Cip. Among the 23 tested isolates with RS-Cip, the qnrS gene was detected in 17/23 (73.9%) and single gyrA mutations were detected in 6/23 (26.1%) (Asp87Tyr [n = 3], Asp87Asn [n = 2], and Ser83Phe [n = 1]). A parC (Thr57Ser) mutation was detected in 13/23 (56.5%) isolates, coexisting with either a qnrS gene or a gyrA mutation. The high incidence of the qnrS gene among isolates with RS-Cip needs to be monitored because qnr genes can spread via plasmids and aid in the emergence of increased resistance levels.

  18. Chronic mucus hypersecretion

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; von Linstow, Marie-Louise; Nepper-Christensen, Steen;

    2005-01-01

    To investigate if chronic mucus hypersecretion (CMH) can be used as a marker of asthma in young adults.......To investigate if chronic mucus hypersecretion (CMH) can be used as a marker of asthma in young adults....

  19. Chronic Diarrhea in Children

    Science.gov (United States)

    ... can include cramping abdominal pain nausea or vomiting fever chills bloody stools Children with chronic diarrhea who have ... can include cramping, abdominal pain, nausea or vomiting, fever, chills, or bloody stools. Children with chronic diarrhea who ...

  20. Chronic inflammatory demyelinating polyneuropathy

    Science.gov (United States)

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... CIDP is one cause of damage to nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy ...

  1. Chronic fatigue syndrome

    Science.gov (United States)

    Bennett RM. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 274. Engleberg NC. Chronic ...

  2. "Chronic Lyme Disease"

    Science.gov (United States)

    ... Content Marketing Share this: Main Content Area "Chronic Lyme Disease" What is "chronic Lyme disease?" Lyme disease is an infection caused by ... J Med 357:1422-30, 2008). How is Lyme disease treated? For early Lyme disease, a short ...

  3. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  4. mCLCA3 modulates IL-17 and CXCL-1 induction and leukocyte recruitment in murine Staphylococcus aureus pneumonia.

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    Kristina Dietert

    Full Text Available The human hCLCA1 and its murine ortholog mCLCA3 (calcium-activated chloride channel regulators are exclusively expressed in mucus cells and linked to inflammatory airway diseases with increased mucus production, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Both proteins have a known impact on the mucus cell metaplasia trait in these diseases. However, growing evidence points towards an additional role in innate immune responses. In the current study, we analyzed Staphylococcus aureus pneumonia, an established model to study pulmonary innate immunity, in mCLCA3-deficient and wild-type mice, focusing on the cellular and cytokine-driven innate inflammatory response. We compared clinical signs, bacterial clearance, leukocyte immigration and cytokine responses in the bronchoalveolar compartment, as well as pulmonary vascular permeability, histopathology, mucus cell number and mRNA expression levels of selected genes (mClca1 to 7, Muc5ac, Muc5b, Muc2, Cxcl-1, Cxcl-2, Il-17. Deficiency of mCLCA3 resulted in decreased neutrophilic infiltration into the bronchoalveolar space during bacterial infection. Only the cytokines IL-17 and the murine CXCL-8 homolog CXCL-1 were decreased on mRNA and protein levels during bacterial infection in mCLCA3-deficient mice compared to wild-type controls. However, no differences in clinical outcome, histopathology or mucus cell metaplasia were observed. We did not find evidence for regulation of any other CLCA homolog that would putatively compensate for the lack of mCLCA3. In conclusion, mCLCA3 appears to modulate leukocyte response via IL-17 and murine CXCL-8 homologs in acute Staphylococcus aureus pneumonia which is well in line with the proposed function of hCLCA1 as a signaling molecule acting on alveolar macrophages.

  5. Prostaglandins and chronic inflammation

    OpenAIRE

    Aoki, Tomohiro; Narumiya, Shuh

    2012-01-01

    Chronic inflammation is the basis of various chronic illnesses including cancer and vascular diseases. However, much has yet to be learned how inflammation becomes chronic. Prostaglandins (PGs) are well established as mediators of acute inflammation, and recent studies in experimental animals have provided evidence that they also function in transition to and maintenance of chronic inflammation. One role PGs play in such processes is amplification of cytokine signaling. As such, PGs can facil...

  6. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-01-01

    Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

  7. Chronic Inflammatory Demyelinating Polyneuropathy

    OpenAIRE

    Dimachkie, Mazen M.; Barohn, Richard J.

    2013-01-01

    Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treat...

  8. Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Marilène Binsfeld

    Full Text Available Multiple myeloma (MM is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD.Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor or autologous (Balb/cJ donor transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses.We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses

  9. Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model.

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    Kimberly A Kline

    Full Text Available The epidemiology and bacteriology of urinary tract infection (UTI varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC and/or Group B Streptococcus (GBS, we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10-100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups.

  10. Evidence for a heritable predisposition to Chronic Fatigue Syndrome

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    Bateman Lucinda

    2011-05-01

    Full Text Available Abstract Background Chronic Fatigue Syndrome (CFS came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV or other murine leukemia related retroviruses (MLV might also suggest underlying genetic implications within the host immune system. Methods We present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases. Results We observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p Conclusions These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.

  11. The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus are not downregulated in productively infected cells

    Directory of Open Access Journals (Sweden)

    Eiden Maribeth V

    2011-07-01

    Full Text Available Abstract Background Over the last several decades it has been noted, using a variety of different methods, that cells infected by a specific gammaretrovirus are resistant to infection by other retroviruses that employ the same receptor; a phenomenon termed receptor interference. Receptor masking is thought to provide an earlier means of blocking superinfection, whereas receptor down regulation is generally considered to occur in chronically infected cells. Results We used replication-competent GFP-expressing viruses containing either an amphotropic murine leukemia virus (A-MLV or the gibbon ape leukemia virus (GALV envelope. We also constructed similar viruses containing fluorescence-labeled Gag proteins for the detection of viral particles. Using this repertoire of reagents together with a wide range of antibodies, we were able to determine the presence and availability of viral receptors, and detect viral envelope proteins and particles presence on the cell surface of chronically infected cells. Conclusions A-MLV or GALV receptors remain on the surface of chronically infected cells and are detectable by respective antibodies, indicating that these receptors are not downregulated in these infected cells as previously proposed. We were also able to detect viral envelope proteins on the infected cell surface and infected cells are unable to bind soluble A-MLV or GALV envelopes indicating that receptor binding sites are masked by endogenously expressed A-MLV or GALV viral envelope. However, receptor masking does not completely prevent A-MLV or GALV superinfection.

  12. Anti-inflammatory effects of five commercially available mushroom species determined in lipopolysaccharide and interferon-γ activated murine macrophages.

    Science.gov (United States)

    Gunawardena, Dhanushka; Bennett, Louise; Shanmugam, Kirubakaran; King, Kerryn; Williams, Roderick; Zabaras, Dimitrios; Head, Richard; Ooi, Lezanne; Gyengesi, Erika; Münch, Gerald

    2014-04-01

    Inflammation is a well-known contributing factor to many age-related chronic diseases. One of the possible strategies to suppress inflammation is the employment of functional foods with anti-inflammatory properties. Edible mushrooms are attracting more and more attention as functional foods since they are rich in bioactive compounds, but their anti-inflammatory properties and the effect of food processing steps on this activity has not been systematically investigated. In the present study, White Button and Honey Brown (both Agaricus bisporus), Shiitake (Lentinus edodes), Enoki (Flammulina velutipes) and Oyster mushroom (Pleurotus ostreatus) preparations were tested for their anti-inflammatory activity in lipopolysaccharide (LPS) and interferon-γ (IFN-γ) activated murine RAW 264.7 macrophages. Potent anti-inflammatory activity (IC₅₀portion of the anti-inflammatory activity was lost suggesting that the anti-inflammatory compounds might be susceptible to heating or prone to evaporation. PMID:24262531

  13. Chronic granulomatous disease associated with chronic glomerulonephritis

    DEFF Research Database (Denmark)

    Frifelt, J J; Schønheyder, Henrik Carl; Valerius, Niels Henrik;

    1985-01-01

    A boy with chronic granulomatous disease (CGD) developed glomerulonephritis at the age of 12 years. The glomerulonephritis progressed to terminal uraemia at age 15 when maintenance haemodialysis was started. The clinical course was complicated by pulmonary aspergillosis and Pseudomonas septicaemia...

  14. Effects of the murine skull in optoacoustic brain microscopy.

    Science.gov (United States)

    Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

    2016-01-01

    Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments.

  15. T Cell Integrin Overexpression as a Model of Murine Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yung Raymond L.

    2003-01-01

    Full Text Available Integrin adhesion molecules have important adhesion and signaling functions. They also play a central role in the pathogenesis of many autoimmune diseases. Over the past few years we have described a T cell adoptive transfer model to investigate the role of T cell integrin adhesion molecules in the development of autoimmunity. This report summarizes the methods we used in establishing this murine model. By treating murine CD4+ T cells with DNA hypomethylating agents and by transfection we were able to test the in vitro effects of integrin overexpression on T cell autoreactive proliferation, cytotoxicity, adhesion and trafficking. Furthermore, we showed that the ability to induce in vivo autoimmunity may be unique to the integrin lymphocyte function associated antigen-1 (LFA-1.

  16. Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and have an invasive phenotype in experimentally infected chickens.

    Directory of Open Access Journals (Sweden)

    Bryony N Parsons

    Full Text Available Salmonella enterica serovar Typhimurium Sequence Type (ST 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans. Oral infection of chickens with ST313 isolates D23580 and Q456 resulted in rapid infection of spleen and liver with all birds infected at these sites by 3 days post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98 and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused hepatosplenomegaly, and this was most pronounced in the ST313-infected animals. At 3 and 7 days post-infection, colonization of the gastrointestinal tract was lower in birds infected with the ST313 isolates compared with ST19. Histological examination and expression of CXCL chemokines in the ileum showed that both D23580 (ST313 and 4/74 (ST19 strains caused increased CXCL expression at 3 days post-infection, and this was significantly higher in the ileum of D23580 vs 4/74 infected birds. At 7 days post-infection, reduced chemokine expression occurred in the ileum of the D23580 but not 4/74-infected birds. Histological analysis showed that D23580 infection resulted in rapid inflammation and pathology including villous flattening and fusion at 3 days post-infection, and subsequent resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology at 3 days post-infection. The data presented demonstrate that ST313 is capable of causing invasive disease in a non-human host. The rapid invasive nature of infection in the chicken, coupled with lower gastrointestinal colonization, supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium that has evolved to become a systemic pathogen that can cause disease in several hosts.

  17. Generation of a safety enhanced Salmonella Gallinarum ghost using antibiotic resistance free plasmid and its potential as an effective inactivated vaccine candidate against fowl typhoid.

    Science.gov (United States)

    Jawale, Chetan V; Chaudhari, Atul A; Lee, John Hwa

    2014-02-19

    A safety enhanced Salmonella Gallinarum (SG) ghost was constructed using an antibiotic resistance gene free plasmid and evaluated its potential as fowl typhoid (FT) vaccine candidate. The antibiotic resistance free pYA3342 plasmid possesses aspartate semialdehyde dehydrogenase gene which is complimentary to the deletion of the chromosomal asd gene in the bacterial host. This plasmid was incorporated with a ghost cassette containing the bacteriophage PhiX174 lysis gene E, designated as pJHL101. The plasmid pJHL101 was transformed into a two virulence genes-deleted SG. The SG ghosts with tunnel formation and loss of cytoplasmic contents were observed by scanning electron microscopy and transmission electron microscopy. The cell viability of the culture solution was decreased to 0% at 24h after the induction of gene E expression by an increase in temperature from 37°C to 42°C. The safety and protective efficacy of the SG ghost vaccine was further examined in chickens which were divided into three groups: group A (non-immunized control), group B (orally immunized), and group C (intramuscularly immunized). The birds were immunized at 7d of age. No clinical symptoms associated with FT such as anorexia, depression and greenish diarrhea were observed in the immunized chickens. Upon challenge with a virulent SG strain at 3 week post-immunization, the chickens immunized with the SG ghost via various routes were efficiently protected, as shown by significantly lower mortality and post-mortem lesions in comparison with control group. In addition, all the immunized chickens showed significantly higher antibody responses accompanied by a potent antigen-specific lymphocyte proliferative response along with significantly increased numbers of CD4⁺ and CD8⁺ T lymphocytes. Overall, our results provide a promising approach of generating SG ghosts using the antibiotic resistance free plasmid in order to prepare a non-living bacterial vaccine candidate which could be

  18. Heterogeneity of multifunctional IL-17A producing S. Typhi-specific CD8+ T cells in volunteers following Ty21a typhoid immunization.

    Directory of Open Access Journals (Sweden)

    Monica A McArthur

    Full Text Available Salmonella enterica serovar Typhi (S. Typhi, the causative agent of typhoid fever, continues to cause significant morbidity and mortality world-wide. CD8+ T cells are an important component of the cell mediated immune (CMI response against S. Typhi. Recently, interleukin (IL-17A has been shown to contribute to mucosal immunity and protection against intracellular pathogens. To investigate multifunctional IL-17A responses against S. Typhi antigens in T memory subsets, we developed multiparametric flow cytometry methods to detect up to 6 cytokines/chemokines (IL-10, IL-17A, IL-2, interferon-γ (IFN-γ, tumor necrosis factor-α (TNF-α and macrophage inflammatory protein-1β (MIP-1β simultaneously. Five volunteers were immunized with a 4 dose regimen of live-attenuated S. Typhi vaccine (Ty21a, peripheral blood mononuclear cells (PBMC were isolated before and at 11 time points after immunization, and CMI responses were evaluated. Of the 5 immunized volunteers studied, 3 produced detectable CD8+ T cell responses following stimulation with S. Typhi-infected autologous B lymphoblastoid cell lines (B-LCL. Additionally, 2 volunteers had detectable levels of intracellular cytokines in response to stimulation with S. Typhi-infected HLA-E restricted cells. Although the kinetics of the responses differed among volunteers, all of the responses were bi- or tri-phasic and included multifunctional CD8+ T cells. Virtually all of the IL-17A detected was derived from multifunctional CD8+ T cells. The presence of these multifunctional IL-17A+ CD8+ T cells was confirmed using an unsupervised analysis program, flow cytometry clustering without K (FLOCK. This is the first report of IL-17A production in response to S. Typhi in humans, indicating the presence of a Tc17 response which may be important in protection. The presence of IL-17A in multifunctional cells co-producing Tc1 cytokines (IL-2, IFN-γ and TNF-α may also indicate that the distinction between Tc17 and

  19. Induction of deletion mutation onompR gene ofSalmonella enterica serovar Typhi isolates from asymptomatic typhoid carriers to evolve attenuated strains for vaccine development

    Institute of Scientific and Technical Information of China (English)

    Senthilkumar B; Anbarasu K; Senbagam D; Rajasekarapandian M

    2014-01-01

    Objective:To develop attenuated strains ofSalmonella enterica serovar Typhi(S. typhi) for the candidate vaccine by osmolar stress.Methods:S. typhiSS3 andSS5 strains were isolated from asymptomatic typhoid carriers inNamakkal,TamilNadu,India.Both strains were grown inLB (LuriaBertani) medium supplemented with various concentration ofNaCl(0.1-0.7M) respectively. The effect of osmolar stress was determined at molecular level byPCR usingMGR06 andMGR 07 primers corresponding to ompR with chromosomalDNA of S. typhiSS3 andSS5 strains. Attenuation by osmolar stress results in deletion mutation of theS. typhi strains was determined by agglutination assays, precipitation method,SDSPAGE analysis and by animal models. Results:The799 bp amplifiedompRgene product from wild typeS. typhiSS3 andSS5 illustrate the presence of virulent gene.Interestingly, there was only a282 bp amplified product fromS. typhiSS3 andSS5 grown in the presence of0.5,0.6 and0.7MNaCl.This illustrates the occurrence of deletion mutation inompRgene at high concentration ofNaCl.Furthermore, both the wild-type and mutantS. typhi outer membraneSDS-PAGE profile reveals the differences in the expression ofompF,ompC andompA proteins.In mice, wild type and mutant strains lethal dose (LD50) were determined.The mice died within72 h when both the wild type strains were injected intraperitoneally with3 logCFU.mL-1.When the mice were injected with the mutants in same dosage, no clinical symptoms were observed; whereas the serum antibody titre was elicited within two weeks indicated that the mutants have the ability to induce protective humoral immune response.These results suggest thatS. typhiSS3 andSS5 may be used as good candidate strains for the development of live attenuated vaccine against salmonellosis.Conclusions:This study demonstrates that theS. typhistrains were attenuated and could be good vaccine candidates in future.

  20. The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines.

    Science.gov (United States)

    Thiem, Vu Dinh; Lin, Feng-Ying C; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W; Robbins, John B; Schneerson, Rachel; Szu, Shousun C

    2011-05-01

    Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

  1. Pharmacodynamics of Fluconazole in a Murine Model of Systemic Candidiasis

    OpenAIRE

    Louie, Arnold; Drusano, George L.; Banerjee, Partha; Liu, Qing-Feng; Liu, Weiguo; Kaw, Pamela; Shayegani, Mehdi; Taber, Harry; Miller, Michael H.

    1998-01-01

    In this study we defined the pharmacodynamic parameter that optimizes outcome in deep-seated Candida albicans infections treated with fluconazole. Using a murine model of systemic candidiasis, we conducted single-dose dose-ranging studies with fluconazole to determine the dosage of this drug that resulted in a 50% reduction in fungal densities (50% effective dose [ED50]) in kidneys versus the fungal densities in the kidneys of untreated controls. We found that the ED50 of fluconazole given in...

  2. A Murine Model of Contact Lens–Associated Fusarium Keratitis

    OpenAIRE

    Sun, Yan; Chandra, Jyotsna; Mukherjee, Pranab; Szczotka-Flynn, Loretta; Ghannoum, Mahmoud A.; Pearlman, Eric

    2010-01-01

    The 2006 outbreak of contact lens–associated Fusarium keratitis resulted in more than 300 cases in the United States in which a commercial lens care product was implicated. In the current study, Fusarium grown as biofilm on silicone hydrogel lenses induced keratitis in a murine model and severity of disease and survival of the organisms were dependent on MyD88, IL-1R1, and TLR4.

  3. Integration of murine leukemia virus DNA depends on mitosis.

    OpenAIRE

    Roe, T.; Reynolds, T. C.; Yu, G.; Brown, P O

    1993-01-01

    In synchronized rat or mouse cells infected with Moloney murine leukemia virus (MLV), integration of viral DNA and production of viral proteins occur only after the cells traverse mitosis. Integration is blocked when cells are prevented from progressing through mitosis. Viral nucleoprotein complexes isolated from arrested cells contain full-length viral DNA and can integrate this viral DNA in vitro, showing that the block to integration in arrested cells is not due to a lack of mature integra...

  4. Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

    OpenAIRE

    Ryder, Alex B.; Zimring, James C.; Hendrickson, Jeanne E

    2014-01-01

    Red blood cell (RBC) alloimmunization may occur following transfusion or pregnancy/delivery. Although observational human studies have described the immunogenicity of RBC antigens and the clinical significance of RBC alloantibodies, studies of factors influencing RBC alloimmunization in humans are inherently limited by the large number of independent variables involved. This manuscript reviews data generated in murine models that utilize transgenic donor mice, which express RBC-specific model...

  5. Lactobacillus rhamnosus GG as an Effective Probiotic for Murine Giardiasis

    OpenAIRE

    Nisha Goyal; Ram Prakash Tiwari; Geeta Shukla

    2011-01-01

    The gut microflora is an important constituent in the intestinal mucosal barrier and has been introduced as the concept of probiotic therapy that beneficially affects the host by improving its intestinal microbial balance. Therefore, the main objective of the study was to explore the protective potential of various lactobacilli strains for murine giardiasis. By experimentation, it was found that the probiotic supplementation of either Lactobacillus casei, L. acidophilus, L. plantarum, or L. r...

  6. Characterization of murine macrophages from bone marrow, spleen and peritoneum

    OpenAIRE

    Wang Changqi; Yu Xiao; Cao Qi; Wang Ya; Zheng Guoping; Tan Thian Kui; Zhao Hong; Zhao Ye; Wang Yiping; Harris David CH

    2013-01-01

    Abstract Background Macrophages have heterogeneous phenotypes and complex functions within both innate and adaptive immune responses. To date, most experimental studies have been performed on macrophages derived from bone marrow, spleen and peritoneum. However, differences among macrophages from these particular sources remain unclear. In this study, the features of murine macrophages from bone marrow, spleen and peritoneum were compared. Results We found that peritoneal macrophages (PMs) app...

  7. Specific receptor binding of staphylococcal enterotoxins by murine splenic lymphocytes.

    OpenAIRE

    Buxser, S; Bonventre, P F; Archer, D L

    1981-01-01

    We describe a reliable assay to measure the specific binding of 125I-labeled staphylococcal enterotoxin A (SEA) by murine spleen cells. Toxin binding by lymphocytes was specific in that it was inhibited by unlabeled SEA but not by unrelated proteins. The biological activity of SEA (T-lymphocyte mitogenesis) correlated with toxin binding to splenic lymphocytes. In the presence of high concentrations of [125I]SEA, specific binding increased rapidly and approached saturation after 2 h. Toxin bin...

  8. High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis independently of obesity.

    Directory of Open Access Journals (Sweden)

    Lisa Gruber

    Full Text Available BACKGROUND: Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis. METHODS: TNF(ΔARE/WT mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors. RESULTS: HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT. Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria. CONCLUSIONS: HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease

  9. Lipid alterations in experimental murine colitis: role of ceramide and imipramine for matrix metalloproteinase-1 expression.

    Directory of Open Access Journals (Sweden)

    Jessica Bauer

    Full Text Available BACKGROUND: Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD. Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS: Chronic colitis was induced by dextran-sulphate-sodium (DSS or transfer of CD4(+CD62L(+ cells into RAG1(-/--mice. Lipid content of isolated murine intestinal epithelial cells (IEC was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM. Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE: Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions.

  10. Antimalarial properties of Artemisia vulgaris L. ethanolic leaf extract in a Plasmodium berghei murine malaria model

    Directory of Open Access Journals (Sweden)

    Gayan S. Bamunuarachchi

    2013-12-01

    Full Text Available Background & objectives: Artemisinin isolated from Artemisia annua is the most potent antimalarial drug against chloroquine-resistant Plasmodium falciparum malaria. Artemisia vulgaris, an invasive weed, is the only Artemisia species available in Sri Lanka. A pilot study was undertaken to investigate the antiparasitic activity of an A. vulgaris ethanolic leaf extract (AVELE in a P. berghei ANKA murine malaria model that elicits pathogenesis similar to falciparum malaria. Methods: A 4-day suppressive and the curative assays determined the antiparasitic activity of AVELE using four doses (250, 500, 750 and 1000 mg/kg, Coartem® as the positive control and 5% ethanol as the negative control in male ICR mice infected with P. berghei. Results: The 500, 750 and 1000 mg/kg doses of AVELE significantly (p ≤0.01 inhibited parasitaemia by 79.3, 79.6 and 87.3% respectively, in the 4-day suppressive assay, but not in the curative assay. Chronic administration of the high dose of AVELE ruled out overt signs of toxicity and stress as well as hepatotoxicity, renotoxicity and haematotoxicity. Interpretation & conclusion: The oral administration of a crude ethonolic leaf extract of A. vulgaris is non-toxic and possesses potent antimalarial properties in terms of antiparasitic activity.

  11. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

    Directory of Open Access Journals (Sweden)

    Daniel Scheiber

    2015-08-01

    Full Text Available Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7 supplementation (100 µg/g diet on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05 and myocardial (2.4 fold; p < 0.05 calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01. MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA expression (10-fold; p < 0.05. CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

  12. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease.

    Science.gov (United States)

    Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

    2014-01-01

    Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients. PMID:24269813

  13. The adaptor molecule Trif contributes to murine host defense during Leptospiral infection.

    Science.gov (United States)

    Jayaraman, Priya A; Devlin, Amy A; Miller, Jennifer C; Scholle, Frank

    2016-09-01

    Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon β (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif(-/-) mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif(-/-) mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans. PMID:27259371

  14. Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I

    Energy Technology Data Exchange (ETDEWEB)

    Angileri, Francesca; Morrow, Geneviève; Roy, Vincent; Orejuela, Diana; Tanguay, Robert M., E-mail: robert.tanguay@ibis.ulaval.ca [Laboratory of Cell and Developmental Genetics, Department of Molecular Biology, Medical Biochemistry and Pathology, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, 1030 avenue de la médecine, Université Laval, Québec G1V 0A6 (Canada)

    2014-04-23

    Hereditary Tyrosinemia type 1 (HT1) is a metabolic liver disease caused by genetic defects of fumarylacetoacetate hydrolase (FAH), an enzyme necessary to complete the breakdown of tyrosine. The severe hepatic dysfunction caused by the lack of this enzyme is prevented by the therapeutic use of NTBC (2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione). However despite the treatment, chronic hepatopathy and development of hepatocellular carcinoma (HCC) are still observed in some HT1 patients. Growing evidence show the important role of heat shock proteins (HSPs) in many cellular processes and their involvement in pathological diseases including cancer. Their survival-promoting effect by modulation of the apoptotic machinery is often correlated with poor prognosis and resistance to therapy in a number of cancers. Here, we sought to gain insight into the pathophysiological mechanisms associated with liver dysfunction and tumor development in a murine model of HT1. Differential gene expression patterns in livers of mice under HT1 stress, induced by drug retrieval, have shown deregulation of stress and cell death resistance genes. Among them, genes coding for HSPB and HSPA members, and for anti-apoptotic BCL-2 related mitochondrial proteins were associated with the hepatocarcinogenetic process. Our data highlight the variation of stress pathways related to HT1 hepatocarcinogenesis suggesting the role of HSPs in rendering tyrosinemia-affected liver susceptible to the development of HCC.

  15. Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and the Safety of the Blood Supply.

    Science.gov (United States)

    Johnson, Andrew D; Cohn, Claudia S

    2016-10-01

    In 2006, a new virus, xenotropic murine leukemia virus-related virus (XMRV), was discovered in a cohort of U.S. men with prostate cancer. Soon after this initial finding, XMRV was also detected in samples from patients with chronic fatigue syndrome (CFS). The blood community, which is highly sensitive to the threat of emerging infectious diseases since the HIV/AIDS crisis, recommended indefinite deferral of all blood donors with a history of CFS. As XMRV research progressed, conflicting results emerged regarding the importance of this virus in the pathophysiology of prostate cancer and/or CFS. Molecular biologists traced the development of XMRV to a recombination event in a laboratory mouse that likely occurred circa 1993. The virus was propagated via cell lines derived from a tumor present in this mouse and spread through contamination of laboratory samples. Well-controlled experiments showed that detection of XMRV was due to contaminated samples and was not a marker of or a causal factor in prostate cancer or CFS. This paper traces the development of XMRV in the prostate and CFS scientific communities and explores the effect it had on the blood community. PMID:27358491

  16. Evaluation of VT-1161 for Treatment of Coccidioidomycosis in Murine Infection Models.

    Science.gov (United States)

    Shubitz, Lisa F; Trinh, Hien T; Galgiani, John N; Lewis, Maria L; Fothergill, Annette W; Wiederhold, Nathan P; Barker, Bridget M; Lewis, Eric R G; Doyle, Adina L; Hoekstra, William J; Schotzinger, Robert J; Garvey, Edward P

    2015-12-01

    Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC50 and MIC90 values of 1 and 2 μg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection. PMID:26369964

  17. Deletion of Serpina1a, a murine α1-antitrypsin ortholog, results in embryonic lethality.

    Science.gov (United States)

    Wang, Dongmei; Wang, Weimin; Dawkins, Paul; Paterson, Trevor; Kalsheker, Noor; Sallenave, Jean-Michel; Houghton, A McGarry

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States Approximately 1% to 2% of COPD patients suffer from α(1)-antitrypsin (A1AT) deficiency, the major inheritable predisposition to COPD/emphysema. To further study the role of A1AT deficiency in the pathogenesis of COPD/emphysema, the authors attempted to generate null-mutant mice for Serpina1a, 1 of 2 A1AT orthologs in mice. Here the authors show that targeted deletion of Serpina1a results in embryonic lethality prior to 8.5 days post conception (dpc). The results are surprising given that A1AT-null humans exist and therefore do not require this gene product for normal development. The Serpina1 gene cluster is substantially different between mouse and man. Through gene duplication, mice have 3 to 5 (depending on the strain) highly homologous proteinase inhibiting (Pi) genes, 2 of which inhibit neutrophil elastase. Despite the abundance of Pi genes in mice, Serpina1a serves a critical, nonredundant function during early mouse development. A1AT-deficient mice have been highly sought after to study emphysema, cancer, and liver disease, and as a model to perfect gene replacement therapy. These results highlight important differences between human and murine serpins and point to the difficulty inherent to using gene-targeted mice to study this common human genetic disease. PMID:21574874

  18. Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease.

    Science.gov (United States)

    Wilkin, Richard J W; Lalor, Patricia F; Parker, Richard; Newsome, Philip N

    2016-04-01

    Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice. PMID:26835538

  19. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification.

    Science.gov (United States)

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L; Potthoff, Sebastian A; Kelm, Malte; Schurgers, Leon J; Westenfeld, Ralf

    2015-08-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p alkaline phosphatase levels (2.2 fold; p alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  20. Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I

    Directory of Open Access Journals (Sweden)

    Francesca Angileri

    2014-04-01

    Full Text Available Hereditary Tyrosinemia type 1 (HT1 is a metabolic liver disease caused by genetic defects of fumarylacetoacetate hydrolase (FAH, an enzyme necessary to complete the breakdown of tyrosine. The severe hepatic dysfunction caused by the lack of this enzyme is prevented by the therapeutic use of NTBC (2-[2-nitro-4-(trifluoromethylbenzoyl] cyclohexane-1,3-dione. However despite the treatment, chronic hepatopathy and development of hepatocellular carcinoma (HCC are still observed in some HT1 patients. Growing evidence show the important role of heat shock proteins (HSPs in many cellular processes and their involvement in pathological diseases including cancer. Their survival-promoting effect by modulation of the apoptotic machinery is often correlated with poor prognosis and resistance to therapy in a number of cancers. Here, we sought to gain insight into the pathophysiological mechanisms associated with liver dysfunction and tumor development in a murine model of HT1. Differential gene expression patterns in livers of mice under HT1 stress, induced by drug retrieval, have shown deregulation of stress and cell death resistance genes. Among them, genes coding for HSPB and HSPA members, and for anti-apoptotic BCL-2 related mitochondrial proteins were associated with the hepatocarcinogenetic process. Our data highlight the variation of stress pathways related to HT1 hepatocarcinogenesis suggesting the role of HSPs in rendering tyrosinemia-affected liver susceptible to the development of HCC.

  1. Cloning and characterization of a murine SIL gene

    Energy Technology Data Exchange (ETDEWEB)

    Collazo-Garcia, N.; Scherer, P.; Aplan, P.D. [Roswell Park Cancer Institute, Buffalo, NY (United States)

    1995-12-10

    The human SIL gene is disrupted by a site-specific interstitial deletion in 25% of children with T-cell acute lymphoblastic leukemia. Since transcriptionally active genes are prone to recombination events, the recurrent nature of this lesion suggests that the SIL gene product is transcriptionally active in the cell type that undergoes this interstitial deletion and that the SIL gene product may play a role in normal lymphoid development. To facilitate studies of SIL gene function, we have cloned and characterized a murine SIL gene. The predicted murine SIL protein is 75% identical to the human gene, with good homology throughout the open reading frame. An in vitro translated SIL cDNA generated a protein slightly larger than the predicted 139-kDa protein. Although a prior report detected SIL mRNA expression exclusively in hematopoietic tissues, a sensitive RT-PCR assay demonstrated SIL expression to be ubiquitous, detectable in all tissues examined. Since the RT-PCR assay suggested that SIL mRNA expression was higher in rapidly proliferating tissues, we assayed SIL mRNA expression using a murine erythroleukemia model of terminal differentiation and found it to be dramatically decreased in conjunction with terminal differentiation. These studies demonstrate that the human SIL gene product is quite well conserved in rodents and suggest that the SIL gene product may play a role in cell proliferation. 26 refs., 6 figs.

  2. Activation of murine macrophages and lymphocytes by Ureaplasma diversum.

    Science.gov (United States)

    Chelmonska-Soyta, A; Miller, R B; Ruhnke, L; Rosendal, S

    1994-01-01

    Ureaplasma diversum is a pathogen in the bovine reproductive tract. The objective of the research was to study interactions with macrophages and lymphocytes which might elucidate aspects of pathogenetic mechanisms of this organism. We studied the activation of murine macrophages of C3H/HeN (LPS-responder) and C3H/HeJ (LPS-low-responder) genotype for TNF-alpha, IL-6, IL-1 and nitric oxide production and blastogenic response of C3H/HeJ splenocytes after Ureaplasma diversum stimulation. Live and heat-killed U. diversum induced TNF-alpha, IL-6 and IL-1 in peritoneal macrophage cultures of both C3H/HeN and C3H/HeJ mice in a dose dependent manner. Interferon-gamma modulated the cytokine production, by increasing the production of TNF-alpha, IL-6 and nitric oxide, but IL-1 secretion was only enhanced in C3H/HeJ macrophages stimulated by live ureaplasmas. Supernatant of U. diversum sonicate was mitogenic for murine spleen lymphocytes. The blastogenic response was dose dependent, and stimulation with both U. diversum and Concanavalin A seemed to have an additive effect. These results suggest that U. diversum, similar to other mycoplasmas, activates murine macrophages and lymphoid cells. The studies should be repeated with bovine cells in order to elucidate pathogenetic aspects of inflammation in cattle caused by U. diversum. PMID:7889459

  3. Chronic penile strangulation

    OpenAIRE

    Lopes, Roberto I.; Silvia I Lopes; Roberto N. Lopes

    2003-01-01

    Chronic penile strangulation is exceedingly rare with only 5 cases previously reported. We report an additional case of progressive penile lymphedema due to chronic intermittent strangulation caused by a rubber band applied to the penile base for 6 years. A 49-year-old man presented incapacity to exteriorize the glans penis. For erotic purposes, he had been using a rubber-enlarging band placed in the penile base for 6 years. With chronic use, he noticed that his penis swelled. Physical examin...

  4. Chronic obstructive pulmonary disease

    OpenAIRE

    NR Anthonisen

    2007-01-01

    The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are...

  5. Optimization of Gene Transfection in Murine Myeloma Cell Lines using Different Transfection Reagents

    OpenAIRE

    Shabani, Mahdi; Hemmati, Sheyda; Hadavi, Reza; Amirghofran, Zahra; Jeddi-Tehrani, Mahmood; Rabbani, Hodjatallah; Shokri, Fazel

    2010-01-01

    Purification and isolation of cellular target proteins for monoclonal antibody (MAb) production is a difficult and time-consuming process. Immunization of mice with murine cell lines stably transfected with genes coding for xenogenic target molecules is an alternative method for mouse immunization and MAb production. Here we present data on transfection efficiency of some commercial reagents used for transfection of murine myeloma cell lines. Little is known about transfectability of murine m...

  6. Murine eosinophil differentiation factor. An eosinophil-specific colony- stimulating factor with activity for human cells

    OpenAIRE

    1986-01-01

    A purified murine lymphokine, eosinophil differentiation factor (EDF), was found to be a selective stimulus for the clonal proliferation and differentiation of murine eosinophil progenitor cells, establishing it as the murine eosinophil colony-stimulating factor (Eo-CSF). EDF was also active on human eosinophil progenitors and mature blood eosinophils, but had no effect on neutrophil or macrophage precursor cells, nor on blood neutrophils. In culture of human bone marrow cells, EDF stimulated...

  7. Etiological characteristics of diarrhea patients with non-typhoidal Salmonella infections in a general hospital%综合医院非伤寒沙门菌感染腹泻患者病原学分析

    Institute of Scientific and Technical Information of China (English)

    兰海丽; 张秀明; 冯雪琴; 严海忠; 卢兰芬; 吴秀娟; 孙各琴; 慕月晶; 王娟; 唐国芳

    2014-01-01

    目的:了解综合医院腹泻患者非伤寒沙门菌感染情况,分析非伤寒沙门菌的血清分型、耐药性和分子特征。方法对2009年9月-2011年6月腹泻病患者送检的767份粪便标本进行非伤寒沙门菌检测,对分离到的菌株进行血清分型、药物敏感性试验和脉冲场凝胶电泳(PFGE)分型。结果从767份腹泻粪便标本中分离到36株非伤寒沙门菌,阳性检出率为4.56%;以儿童为主,占65.71%;共分为10种血清型,主要以鼠伤寒沙门菌和肠炎沙门菌为主,分别占37.14%和28.57%;10个血清型非伤寒沙门菌对头孢类和环丙沙星的敏感率>84.00%,除斯坦利沙门菌和山夫登宝沙门菌外,其他血清型均对多种抗菌药物产生不同程度的耐药或交叉耐药;将13株鼠伤寒沙门菌和10株肠炎沙门菌共分离出19个PFGE分型,其中2株肠炎沙门菌PFGE同型,3株鼠伤寒沙门菌PFGE同型,存在不同耐药谱。结论综合医院引起感染性腹泻的非伤寒沙门菌主要为鼠伤寒沙门菌和肠炎沙门菌,儿童多见;非伤寒沙门菌多药耐药严重,临床在应用氟喹诺酮类治疗非肠外沙门菌属感染时,应根据药敏结果慎重选择。%OBJECTIVE To understand the incidence of non-typhoid Salmonell infections in the diarrhea patients from a general hospital and then analyze the serotypes ,drug resistance as well as the molecular characteristics of the non-typhoidal Salmonella strains .METHODS Totally 767 feces specimens obtained from the diarrhea patients from Sep 2009 to Jun 2011 were detected for the non-typhoidal Salmonella strains ,then the serotyping ,drug sus-ceptibility testing ,and pulsed field gel electrophoresis (PFGE) assay were performed for the isolated strains . RESULTS A total of 36 strains of non-typhoidal Salmonella were isolated from 767 copies of feces specimens with the positive detection rate of 4 .56% ,among which 65 .71% were

  8. Effects of the flavanone combination hesperetin-naringenin, and orange and grapefruit juices, on airway inflammation and remodeling in a murine asthma model.

    Science.gov (United States)

    Seyedrezazadeh, Ensiyeh; Kolahian, Saeed; Shahbazfar, Amir-Ali; Ansarin, Khalil; Pour Moghaddam, Masoud; Sakhinia, Masoud; Sakhinia, Ebrahim; Vafa, Mohammadreza

    2015-04-01

    We investigated whether flavanones, hesperetin-naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non-asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra-alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM-induced asthma.

  9. Chronic diseases in adolescence

    Directory of Open Access Journals (Sweden)

    Rončević Nevenka

    2006-01-01

    Full Text Available Introduction. The prevalence of chronic diseases in adolescence is constantly increasing, especially in the last two decades. Adolescence is a period of important changes: body growth and development, sexual development, development of cognitive abilities, change in family relations and between peers, formation of personal identity and personal system of values, making decisions on future occupation etc. Chronic diseases in adolescence. Chronic disorders affect all development issues and represent an additional burden for adolescents. The interaction between chronic disorders and various development issues is complex and two-way: the disease may affect development, and development may affect the disease. Developmental, psychosocial and family factors are of great importance in the treatment of adolescents with chronic disorders. Chronic disorders affect all aspects of adolescent life, including relations with peers, school, nutrition, learning, traveling, entertainment, choice of occupation, plans for the future. Physicians should keep in mind that chronic diseases and their treatment represent only one aspect of person's life. Adolescents with chronic diseases have other needs as well, personal priorities, social roles and they expect these needs to be recognized and respected. Adolescent health care should be adjusted to the life style of adolescents.

  10. Managing your chronic pain

    Science.gov (United States)

    ... your chronic back pain To use the sharing features on this page, please enable JavaScript. Managing chronic pain means finding ways to make your back pain tolerable so you can live your life. You may not be able to ...

  11. 用文献综述法估计我国食源性非伤寒沙门氏菌病疾病负担%Estimation on disease burden of foodborne non-typhoid salmonellosis in China using literature review method

    Institute of Scientific and Technical Information of China (English)

    毛雪丹; 胡俊峰; 刘秀梅

    2011-01-01

    Objective To estimate the disease burden of foodborne non-typhoid salmonellosis in China. Methods The occurrence rate of acute diarrhea and the proportion of non-typhoid salmonella were evaluated by literature reviews.The occurence rate of foodborne non-typhoid salmonellosis was calculated by the acute diarrhea morbidity multiplied the factors, including the proportion of non-typhoid salmonella among the diarrhea cases, the diarrhea proportion among the non-typhoid salmonellosis cases from National Foodborne Disease Monitoring Network, foodborne proportion of non-typhoid salmonella infection. The death information was obtained from the third report of death investigation in China from MOH. Results During 2000 - 2009, non-typhoid salmonella annually caused 8 235 000 diarrhea cases, from which 9 874 000 gastroenteritis cases were deduced, 9 035 000 cases were infected by food transmission. Annually 792 deaths were estimated. Conclusions Non-typhoid salmonella is still one of the main foodborne pathgens in our country and causes heavy burden on China. The proportion of non-typhoid salmonellosis cases among gastroenteritis is similar to developed countries in China, and the fatality rate is lower than developed countries. There's some gap between the method by literatures review in China and the well-designed laboratory surveillance. Therefore, the foodborne disease active surveillance including laboratories surveillance should be set up.%目的 估计我国食源性非伤寒沙门氏菌病造成的疾病负担,为我国食源性疾病主动监测网络的建立提供依据.方法 利用文献综述方法 估计我国急性腹泻发病率以及腹泻人群中非伤寒沙门氏菌的比例,利用食源性疾病监测网获得非伤寒沙门氏菌感染患者的腹泻发生比例,利用文献综述获得非伤寒沙门氏菌的食源性比例.综合腹泻发病率及各项乘数获得食源性非伤寒沙门氏菌病的发病率.利用卫生部第三次死因调查报

  12. CD69 expression on airway eosinophils and airway inflammation in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-ying; SHEN Hua-hao; James J Lee; Nancy A Lee

    2006-01-01

    Background Asthma is a chronic airway disease with inflammation characterized by physiological changes(airway hyper-responsiveness, AHR) and pathological changes (inflammatory cells infiltration and mucus production). Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice.Methods Eosinophils from peripheral blood of IL-5 transgenic mice (NJ.1638) were purified. Mice were divided into five groups: wild type mice sensitized and challenged with saline (WS group), wild type mice sensitized and challenged with ovalbumin (WO group), IL-5-/- mice sensitized and challenged with saline and transferred with purified eosinophils (ISE group), IL-5-/- mice sensitized and challenged with OVA and transferred with purified eosinophils (IOE group), IL-5-/- mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody (IOE+antiCD4mAb group).IL-5-/- mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26and 27 purified eosinophils were transferred intratracheally to IL-5-/- mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry.Results Purified eosinophils did not express CD69. But eosinophils cultured with PMA+MA, IFN- γ, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE+antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression

  13. Chronic gastritis - an update.

    Science.gov (United States)

    Varbanova, Mariya; Frauenschläger, Katrin; Malfertheiner, Peter

    2014-12-01

    Helicobacter pylori is the main aetiologic factor for chronic gastritis worldwide. The degree of inflammation and the evolution of this form of chronic gastritis can vary largely depending on bacterial virulence factors, host susceptibility factors and environmental conditions. Autoimmune gastritis is another cause of chronic inflammation in the stomach, which can occur in all age groups. This disease presents typically with vitamin B12 deficiency and pernicious anaemia. The presence of anti-parietal cell antibodies is highly specific for the diagnosis. The role of H. pylori as a trigger for autoimmune gastritis remains uncertain. Other rare conditions for chronic gastritis are chronic inflammatory conditions such as Crohn's disease or on the background of lymphocytic or collagenous gastroenteropathies. PMID:25439069

  14. [Chronic migraine: treatment].

    Science.gov (United States)

    Pascual, Julio

    2012-04-10

    We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A. PMID:22532241

  15. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.

    Science.gov (United States)

    Conley, Melissa N; Wong, Carmen P; Duyck, Kyle M; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

  16. 临沂市消除伤寒副伤寒流行周期的控制对策%Control countermeasures for eliminating epidemic periodiCity of typhoid fever and paratyphoid fever in Linyi City

    Institute of Scientific and Technical Information of China (English)

    刘瑞田

    2012-01-01

    [Objective]To analyze the epidemiologies] characteristics of typhoid fever and paratyphoid fever, make the scientific control countermeasures, so as to eliminate the epidemic periodicity. [Methods]The data of epidemic situation and individual cases of typhoid fever and paratyphoid fever from 1956 to 2011 in Iinyi City were collected, and the epidemiological analysis was conducted by total statistics and time statistics. [Results]There were 12 079 cases of typhoid fever and paratyphoid fever from 1956 to 2011, and the average annual incidence was 2.45/lakh. An epidemic period occurs every 20 years, and the peak season was June to December. 77.72% of patients were people aged 15-40 years old, and 81.75% of cases were farmers, students and workers. The incidence of the disease in plain was higher than that in mountainous area. Now Iinyi is in a sporadic period after the third epidemic period. The average annual incidence dropped to 0.78/lakh during 2005-2011. [ Conclusion]Controlling infectious source, cutting off the transmission route, the epidemic periodicity of typhoid fever and paratyphoid fever of every 20 years in Iinyi City will be controlled.%目的 对临沂市1956-2011年伤寒副伤寒进行流行病学分析,制定科学控制对策,消除流行周期.方法 收集该市1956-2011年伤寒副伤寒疫情及流行病学个案调查资料,采用总和统计和年代统计的方法进行流行病学分析.结果 1956-2011年共计发生伤寒副伤寒12 079例,年均发病率为2.45/10万.发病具有20a左右1次的流行周期,每年6-12月份为多发季节.年龄主要集中在15 ~40岁,占77.72%;农民、学生、工人发病占81.75%,平原发病高于山区.目前该地区已进入第3次流行周期后的散发期,2005-2011年年均发病率已降为0.78/10万.结论 控制传染源,切断传播途径,进一步净化疫情,该市20年左右1次的伤寒副伤寒流行周期可被消除.

  17. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

    Science.gov (United States)

    ... People About NINDS NINDS Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Information Page Table of Contents (click to jump ... en Español What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)? Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological ...

  18. Stages of Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  19. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  20. Nanomechanical phenotype of chondroadherin-null murine articular cartilage.

    Science.gov (United States)

    Batista, Michael A; Nia, Hadi T; Önnerfjord, Patrik; Cox, Karen A; Ortiz, Christine; Grodzinsky, Alan J; Heinegård, Dick; Han, Lin

    2014-09-01

    Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈70-80% reduction in the indentation modulus, Eind, of the superficial zone knee cartilage of 11 weeks, 4 months and 1 year old animals. This mechanical phenotype correlates well with observed increases in the heterogeneity collagen fibril diameters in the surface zone. The results suggest that CHAD mainly plays a major role in regulating the formation of the collagen fibrillar network during the early skeletal development. In contrast, CHAD-deletion had no appreciable effects on the indentation mechanics of middle/deep zone cartilage, likely due to the dominating role of aggrecan in the middle/deep zone. The presence of significant rate dependence of the indentation stiffness in both WT and CHAD(-/-) knee cartilage suggested the importance of both fluid flow induced poroelasticity and intrinsic viscoelasticity in murine cartilage biomechanical properties. Furthermore, the marked differences in the nanomechanical behavior of WT versus CHAD(-/-) cartilage contrasted sharply with the relative absence of overt differences in histological appearance. These observations highlight the sensitivity of nanomechanical tools in evaluating structural and mechanical phenotypes in transgenic mice. PMID:24892719

  1. Characterization of a Novel Murine Model to Study Zika Virus.

    Science.gov (United States)

    Rossi, Shannan L; Tesh, Robert B; Azar, Sasha R; Muruato, Antonio E; Hanley, Kathryn A; Auguste, Albert J; Langsjoen, Rose M; Paessler, Slobodan; Vasilakis, Nikos; Weaver, Scott C

    2016-06-01

    The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain-Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼10(7) plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines. PMID:27022155

  2. Characterization of a Novel Murine Model to Study Zika Virus

    Science.gov (United States)

    Rossi, Shannan L.; Tesh, Robert B.; Azar, Sasha R.; Muruato, Antonio E.; Hanley, Kathryn A.; Auguste, Albert J.; Langsjoen, Rose M.; Paessler, Slobodan; Vasilakis, Nikos; Weaver, Scott C.

    2016-01-01

    The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain–Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼107 plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines. PMID:27022155

  3. PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV and autism

    Directory of Open Access Journals (Sweden)

    Satterfield Brent C

    2010-10-01

    Full Text Available Abstract Xenotropic murine leukemia virus-related virus (XMRV is a retrovirus implicated in prostate cancer and chronic fatigue syndrome (CFS. Press releases have suggested that it could contribute to autism spectrum disorder (ASD. In this study we used two PCR assays and one antibody assay to screen 25 blood samples from autistic children born to mothers with CFS and from 20 mixed controls including family members of the children assayed, people with fibromyalgia and people with chronic Lyme disease. Using a real-time PCR assay, we screened an additional 48 South Carolina autism disorder samples, 96 Italian ASD samples, 61 South Carolina ASD samples and 184 healthy controls. Despite having the ability to detect low copy number XMRV DNA in a large background of cellular DNA, none of the PCR assays found any evidence of XMRV infection in blood cells from patients or controls. Further, no anti-XMRV antibodies were detected, ruling out possible low level or abortive infections in blood or in other reservoirs. These results imply that XMRV is not associated with autism.

  4. Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer.

    Directory of Open Access Journals (Sweden)

    George M Philips

    Full Text Available OBJECTIVE: Chronic fibrosing liver injury is a major risk factor for hepatocarcinogenesis in humans. Mice with targeted deletion of Mdr2 (the murine ortholog of MDR3 develop chronic fibrosing liver injury. Hepatocellular carcinoma (HCC emerges spontaneously in such mice by 50-60 weeks of age, providing a model of fibrosis-associated hepatocarcinogenesis. We used Mdr2(-/- mice to investigate the hypothesis that activation of the hedgehog (Hh signaling pathway promotes development of both liver fibrosis and HCC. METHODS: Hepatic injury and fibrosis, Hh pathway activation, and liver progenitor populations were compared in Mdr2(-/- mice and age-matched wild type controls. A dose finding experiment with the Hh signaling antagonist GDC-0449 was performed to optimize Hh pathway inhibition. Mice were then treated with GDC-0449 or vehicle for 9 days, and effects on liver fibrosis and tumor burden were assessed by immunohistochemistry, qRT-PCR, Western blot, and magnetic resonance imaging. RESULTS: Unlike controls, Mdr2(-/- mice consistently expressed Hh ligands and progressively accumulated Hh-responsive liver myofibroblasts and progenitors with age. Treatment of aged Mdr2-deficient mice with GDC-0449 significantly inhibited hepatic Hh activity, decreased liver myofibroblasts and progenitors, reduced liver fibrosis, promoted regression of intra-hepatic HCCs, and decreased the number of metastatic HCC without increasing mortality. CONCLUSIONS: Hh pathway activation promotes liver fibrosis and hepatocarcinogenesis, and inhibiting Hh signaling safely reverses both processes even when fibrosis and HCC are advanced.

  5. Bacterial-excreted small volatile molecule 2-aminoacetophenone induces oxidative stress and apoptosis in murine skeletal muscle.

    Science.gov (United States)

    Bandyopadhaya, Arunava; Constantinou, Caterina; Psychogios, Nikolaos; Ueki, Ryusuke; Yasuhara, Shingo; Martyn, J A Jeevendra; Wilhelmy, Julie; Mindrinos, Michael; Rahme, Laurence G; Tzika, A Aria

    2016-04-01

    Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial phenotypes that favor chronic infection, while also dampening the pathogen‑induced innate immune response, thus compromising muscle function and promoting host tolerance to infection. In this study, murine whole-genome expression data have demonstrated that 2-AA affects the expression of genes involved in reactive oxygen species (ROS) homeostasis, thus producing an oxidative stress signature in skeletal muscle. The results of the present study demonstrated that the expression levels of genes involved in apoptosis signaling pathways were upregulated in the skeletal muscle of 2-AA-treated mice. To confirm the results of our transcriptome analysis, we used a novel high-resolution magic-angle-spinning (HRMAS), proton (1H) nuclear magnetic resonance (NMR) method and observed increased levels of bisallylic methylene fatty acyl protons and vinyl protons, suggesting that 2-AA induces skeletal muscle cell apoptosis. This effect was corroborated by our results demonstrating the downregulation of mitochondrial membrane potential in vivo in response to 2-AA. The findings of the present study indicate that the bacterial infochemical, 2-AA, disrupts mitochondrial functions by inducing oxidative stress and apoptosis signaling and likely promotes skeletal muscle dysfunction, which may favor chronic/persistent infection.

  6. Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.

    Directory of Open Access Journals (Sweden)

    Rabea A Hall

    Full Text Available The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs with genome-wide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury.

  7. Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.

    Science.gov (United States)

    Hall, Rabea A; Liebe, Roman; Hochrath, Katrin; Kazakov, Andrey; Alberts, Rudi; Laufs, Ulrich; Böhm, Michael; Fischer, Hans-Peter; Williams, Robert W; Schughart, Klaus; Weber, Susanne N; Lammert, Frank

    2014-01-01

    The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL) analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs) with genome-wide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury. PMID:24586654

  8. Purification of Murine Monoclonal IgM Antibody

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    This paper presents the purification of a monoclonal IgM antibody against human tumor associated antigen Lewis-Y by ion exchange chromatography and gel filtration.Enzyme-linked immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (PAGE) were used to identify purified IgM antibody.In flow cytometry analysis, the purified IgM antibody recognizes human breast tumor cell line MCF-7 which expresses Lewis-Y antigen.This work presents a new way for the purification of murine monoclonal IgM antibody.

  9. Protective role of murine norovirus against Pseudomonas aeruginosa acute pneumonia.

    Science.gov (United States)

    Thépaut, Marion; Grandjean, Teddy; Hober, Didier; Lobert, Pierre-Emmanuel; Bortolotti, Perrine; Faure, Karine; Dessein, Rodrigue; Kipnis, Eric; Guery, Benoit

    2015-01-01

    The murine norovirus (MNV) is a recently discovered mouse pathogen, representing the most common contaminant in laboratory mouse colonies. Nevertheless, the effects of MNV infection on biomedical research are still unclear. We tested the hypothesis that MNV infection could alter immune response in mice with acute lung infection. Here we report that co-infection with MNV increases survival of mice with Pseudomonas aeruginosa acute lung injury and decreases in vivo production of pro-inflammatory cytokines. Our results suggest that MNV infection can deeply modify the parameters studied in conventional models of infection and lead to false conclusions in experimental models. PMID:26338794

  10. Adrenaline influences the release of interleukin-6 from murine pituicytes

    DEFF Research Database (Denmark)

    Christensen, J D; Hansen, E W; Frederiksen, C;

    1999-01-01

    In this study, we examined the effect of adrenaline and interleukin-1beta on interleukin-6 secretion from cultured murine neurohypophyseal cells. Cells were cultured from neurohypophyses of 3- to 5-week-old mice and experiments were performed after 13 days in culture. Interleukin-6 was measured...... in 24-h samples using a sandwich fluoroimmunoassay. Unstimulated cells released 19+/-3 fmol interleukin-6/neurohypophysis/24 h (mean +/- S.E.M., n = 42). Adrenaline and interleukin-1beta increased the release of interleukin-6 from the cells in a concentration-dependent manner. Incubation with adrenaline...

  11. Dystrophic Spinal Deformities in a Neurofibromatosis Type 1 Murine Model

    OpenAIRE

    Rhodes, Steven D.; Zhang, Wei; Yang, Dalong; Yang, Hao; Chen, Shi; Wu, Xiaohua; Li, Xiaohong; Yang, Xianlin; Mohammad, Khalid S.; Guise, Theresa A.; Amanda L Bergner; Stevenson, David A.; Yang, Feng-Chun

    2015-01-01

    Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/−;PeriCre and Nf1flox/−;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/−;PeriCre and Nf...

  12. DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ...Sweet MJ, Beasley SJ, Cronau SL, Hume DA. J Leukoc Biol. 1999 Oct;66(4):542-8. (.png) (.svg) (.html) (.csml) Show The action...s of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial D

  13. Typhoid spine - A case report

    Directory of Open Access Journals (Sweden)

    Rajesh P

    2004-01-01

    Full Text Available A case of Salmonella typhi isolated from L4-L5 spine is reported here. The causative organism was not suspected preoperatively. The patient responded favourably to surgical drainage and appropriate antibiotic therapy.

  14. Chronicity and control

    DEFF Research Database (Denmark)

    Whyte, Susan Reynolds

    2012-01-01

    This paper proposes a way of framing the study of ‘noncommunicable diseases’ within the more general area of chronic conditions. Focusing on Africa, it takes as points of departure the situation in Uganda, and the approach to health issues developed by a group of European and African colleagues...... over the years. It suggests a pragmatic analysis that places people's perceptions and practices within a field of possibilities shaped by policy, health care systems, and life conditions. In this field, the dimensions of chronicity and control are the distinctive analytical issues. They lead...... on to consideration of patterns of sociality related to chronic conditions and their treatment....

  15. 新型人类逆转录病毒XMRV研究进展%Research Progress in Xenotropic Murine Leukemia Virus-Related Virus A New Human Retrovirus

    Institute of Scientific and Technical Information of China (English)

    王斌; 杨军; 张苏展; Samson A Chow; 沈肖曹; 张哲; 邓刚; 王丹; 叶剑; 沈学彬; 苏锟楷; 陈欢

    2011-01-01

    异嗜性鼠白血病病毒相关病毒(xenotropic murine leukemia virus-related virus,XMRV)是迄今发现的第一种可以感染人类的γ逆转录病毒.XMRV最初于2006年在RNaseL基因缺陷型的前列腺癌组织中首次被鉴定,其序列与鼠科白血病病毒(murine leukemia virus,MLV)十分相似.目前,北美、欧洲和亚洲的多个研究机构在人类前列腺癌和慢性疲劳综合征(chronic fatigue syndrome,CFS)患者中检测到XMRV.但不同研究间结果差异很大,XMRV感染与人类疾病之间的相关性尚不明确.该文综述了目前XMRV的相关研究进展,包括与人类疾病的关系、XMRV的基本特征、病理生理学可能的机制等方面,并就今后研究趋势和注意问题进行了讨论.%Xenotropic murine leukemia virus-related virus (XMRV) is a new gammaretrovirus that can infect humans. Retroviruses are enveloped, positive-sense RNA viruses that are associated with many diseases, such as neoplasias, immunodeficiencies, and neurological disorders. XMRV was originally identified in prostate cancer patients with a deficiency in the antiviral enzyme Rnase L in 2006. The genome of XMRV is closely related to xenotropic murine leukemia virus (MLV). Recently, several independent groups have detected XMRV in prostate cancer and chronic fatigue syndrome patients, but the results vary greatly. The link between XMRV and human diseases has not been established. This paper presents and summarizes in detail the characteristics of XMRV, association of XMRV with human diseases, and potential mechanisms of XMRV pathophysiology. We also discuss the future research direction, such as the establishment of standard operation procedure and epidemiologic evidence of an association of XMRV with human diseases in large-scale studies.

  16. Scanning electron microscopy of the neuropathology of murine cerebral malaria

    Directory of Open Access Journals (Sweden)

    Brenneis Christian

    2006-11-01

    Full Text Available Abstract Background The mechanisms leading to death and functional impairments due to cerebral malaria (CM are yet not fully understood. Most of the knowledge about the pathomechanisms of CM originates from studies in animal models. Though extensive histopathological studies of the murine brain during CM are existing, alterations have not been visualized by scanning electron microscopy (SEM so far. The present study investigates the neuropathological features of murine CM by applying SEM. Methods C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively. Results Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces. Conclusion The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.

  17. Fluorescence tomography in a murine model of Alzheimer's disease

    Science.gov (United States)

    Raymond, Scott B.; Kumar, Anand T. N.; Dunn, Andrew K.; Boas, David A.; Bacskai, Brian J.

    2007-02-01

    Noninvasive molecular imaging of amyloid plaques in murine Alzheimer's disease models would accelerate drug development and basic Alzheimer's research. Amyloid plaques differ from traditional fluorescent targets in size and spatial distribution and therefore present a unique challenge for biomarker development and tomography. To study imaging feasibility and establish biomarker criteria, we developed a digital mouse head model from a 100 μm-resolution, digital, segmented mouse atlas1. The cortical region of the brain was filled with a spatially uniform distribution of plaques that had different fluorescent properties from the surrounding brain tissue, similar to current transgenic mouse models of Alzheimer's disease. Fluorescence was simulated with a Monte Carlo algorithm using different plaque densities, detection geometries, and background fluorescence. Our preliminary results demonstrated that shielding effects might require nonlinear reconstruction algorithms and that background fluorescence would seriously hinder quantitative burden estimation. The Monte Carlo based approach presented here offers a powerful way to study the feasibility of non-invasive imaging in murine Alzheimer's models and to optimize experimental conditions.

  18. Great efficacy of sulfachloropyrazine-sodium against acute murine toxoplasmosis

    Institute of Scientific and Technical Information of China (English)

    Yan-Bo Zeng; Bing Huang; Shun-Hai Zhu; Hui Dong; Hong-Yu Han; Lian-Lian Jiang; Quan Wang; Jun Cheng; Qi-Ping Zhao; Wei-Jiao Ma

    2012-01-01

    Objective: To identify more effective and less toxic drugs to treat animal toxoplasmosis.Methods:Efficacy of seven kinds of sulfonamides against Toxoplasma gondii (T. gondii) in an acute murine model was evaluated. The mice used throughout the study were randomly assigned to many groups (10 mice each), which either remained uninfected or were infected intraperitoneally with tachyzoites of T. gondii (strains RH and CN). All groups were then treated with different sulfonamides and the optimal treatment protocol was determined candidates. Sulfadiazine-sodium (SD) was used for comparison. Results: The optimal therapy involved gavaging mice twice per day with 250 mg/kg bw of sulfachloropyrazine-sodium (SPZ) for five days. Using this protocol, the average survival time and the time-point of 50% fatalities were prolonged significantly compared with SD treatment. Treatment with SPZ protected 40% of mice from death, and the heart and kidney tissue of these animals was parasite-free, as determined by nested-PCR. SPZ showed excellent therapeutic effects in the treatment of T. gondii in an acute murine model and is therefore a promising drug candidate for the treatment and prevention of T. gondii in animals. Conclusions: It can be concluded that the effective drug sulfachloropyrazine may be the new therapeutic options against animal toxoplasmosis.

  19. Bifidobacteria DNA Induces Murine Macrophages Activation in vitro

    Institute of Scientific and Technical Information of China (English)

    Yalin Li; Xun Qu; Hua Yang; Li Kang; Yingping Xu; Bo Bai; Wengang Song

    2005-01-01

    Previous studies have shown that oligodeoxynucleotides containing unmethylated CpG motifs were used as adjuvants for immunoregulation and immune response. This study was to explore the activation effects of Bifidobacteria DNA containing unmethylated CpG motifs (CpG DNA) on murine macrophage J774A.1 cells. The genomic DNA of Bifidobacteria was extracted and purified, and the methylation degree of CpG motifs was tested.The phagocytic ability of the macrophages was detected by flow cytometry. The cytokines (IL-1β, IL-6, IL-12p40 and TNF-α) levels in the culture supernatants of Bifidobacteria DNA treated J774A.1 cells were assayed by ELISA. The content of nitric oxide (NO) was detected by Griess reagent. After treated with Bifidobacteria DNA for 24h,Nile Red stain increased in J774A.1 macrophage, which suggested that the lipid metabolism increased in the macrophages. The phagocytic ability and levels of NO and cytokines of IL-1β, IL-6, IL-12p40 and TNF-α were significantly higher than PBS group and CT DNA group. The results indicated that Bifidobacteria DNA could activate murine macrophages J774A.1, which could provide scientific basis for the research and application of microorganism DNA preparation.

  20. Chronic Condition Data Warehouse

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Chronic Condition Data Warehouse (CCW) provides researchers with Medicare and Medicaid beneficiary, claims, and assessment data linked by beneficiary across...

  1. Sleep and Chronic Disease

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . Sleep About Us About Sleep Key Sleep Disorders Sleep ... Sheets Data & Statistics Projects and Partners Resources Events Sleep and Chronic Disease Recommend on Facebook Tweet Share ...

  2. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Contact Us Shop FAQs The Art of Pain Management Resources Going to the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs Resource Guide to Chronic Pain Treatments Pain ...

  3. What Is Chronic Pain?

    Medline Plus

    Full Text Available Already a member? Log In or Sign Up Home About Us Support the ACPA Contact Us Shop ... for Understanding Pain September is Pain Awareness Month Home Pain Management Tools Videos What Is Chronic Pain? ...

  4. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... chronic pain there may be no apparent physical injury or illness to explain it. The physician and ... expected period of healing for an illness or injury. You can experience pain even if you are ...

  5. Chronic rhinosinusitis pathogenesis.

    Science.gov (United States)

    Stevens, Whitney W; Lee, Robert J; Schleimer, Robert P; Cohen, Noam A

    2015-12-01

    There are a variety of medical conditions associated with chronic sinonasal inflammation, including chronic rhinosinusitis (CRS) and cystic fibrosis. In particular, CRS can be divided into 2 major subgroups based on whether nasal polyps are present or absent. Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier, and tissue remodeling all contribute to the chronic inflammatory and tissue-deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and might be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review, with special focus placed on the roles of epithelial cells and the host immune response in patients with cystic fibrosis, CRS without nasal polyps, or CRS with nasal polyps. PMID:26654193

  6. Chronic penile strangulation

    Directory of Open Access Journals (Sweden)

    Lopes Roberto I

    2003-01-01

    Full Text Available Chronic penile strangulation is exceedingly rare with only 5 cases previously reported. We report an additional case of progressive penile lymphedema due to chronic intermittent strangulation caused by a rubber band applied to the penile base for 6 years. A 49-year-old man presented incapacity to exteriorize the glans penis. For erotic purposes, he had been using a rubber-enlarging band placed in the penile base for 6 years. With chronic use, he noticed that his penis swelled. Physical examination revealed lymphedema of the penis, phimosis and a stricture in the penile base. The patient was submitted to circumcision and the lymphedema remained stable 10 months postoperatively. Chronic penile incarceration usually causes penile lymphedema and urinary disturbance. Treatment consists of removal of foreign devices and surgical treatment of lymphedema.

  7. Chronic Conditions Dashboard

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Chronic Conditions Dashboard presents statistical views of information on the prevalence, utilization and Medicare spending for Medicare beneficiaries with...

  8. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... after a period of time the spinal cord has changed, after a period of time there are ... absence of an apparent cause. But chronic pain has a physiological or neurological basis even when we ...

  9. Chronic Kidney Disease

    Science.gov (United States)

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  10. Chronic Conditions Chartbook

    Data.gov (United States)

    U.S. Department of Health & Human Services — Chronic Conditions among Medicare Beneficiaries is a chartbook prepared by the Centers for Medicare and Medicaid Services and created to provide an overview of...

  11. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Programs Resource Guide to Chronic Pain Treatments Pain Awareness Toolkits Partners for Understanding Pain September is Pain Awareness Month Home Pain Management Tools Videos What Is ...

  12. Chronic Fatigue Syndrome

    Science.gov (United States)

    Chronic fatigue syndrome (CFS) is a disorder that causes extreme fatigue. This fatigue is not the kind of tired feeling that ... activities. The main symptom of CFS is severe fatigue that lasts for 6 months or more. You ...

  13. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    Directory of Open Access Journals (Sweden)

    Khadilkar Satish

    2011-01-01

    Full Text Available The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP. Pure motor (multifocal motor neuropathy, sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy, exclusively distal sensory (distal acquired demyelinating sensory neuropathy and very proximal sensory (chronic immune sensory polyradiculopathy constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc. have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.

  14. Idiopathic chronic eosinophilic pneumonia

    OpenAIRE

    Cordier Jean-François; Marchand Eric

    2006-01-01

    Abstract Idiopathic chronic eosinophilic pneumonia (ICEP) is characterized by subacute or chronic respiratory and general symptoms, alveolar and/or blood eosinophilia, and peripheral pulmonary infiltrates on chest imaging. Eosinophilia is present in most cases, usually in excess of 1000/mm3. In absence of significant blood eosinophilia, a diagnosis of ICEP is supported by the demonstration of bronchoalveolar lavage eosinophilia. ICEP is typically associated with eosinophil counts higher than ...

  15. Experimental chronic periodontitis morphogenesis

    OpenAIRE

    Schneider S.A.

    2011-01-01

    Morphogenesis of periodontium tissue in a model of chronic periodontitis was studied. Adult Wistar rats wereused in a model; chronic periodontitis was developed through mastication-related loading decrease. Histological assessmentof periodontium tissue was conducted at Days 7, 14, 21 and 30. It was demonstrated that dystrophic tissue changes prevailover the inflammatory one in this particular experimental model. The structural elements of periodontium were involved intothe pathologic process ...

  16. Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Dhawan Gunjan

    2012-07-01

    Full Text Available Abstract Background Microglial activation is an important histologic characteristic of the pathology of Alzheimer’s disease (AD. One hypothesis is that amyloid beta (Aβ peptide serves as a specific stimulus for tyrosine kinase-based microglial activation leading to pro-inflammatory changes that contribute to disease. Therefore, inhibiting Aβ stimulation of microglia may prove to be an important therapeutic strategy for AD. Methods Primary murine microglia cultures and the murine microglia cell line, BV2, were used for stimulation with fibrillar Aβ1-42. The non-receptor tyrosine kinase inhibitor, dasatinib, was used to treat the cells to determine whether Src family kinase activity was required for the Aβ stimulated signaling response and subsequent increase in TNFα secretion using Western blot analysis and enzyme-linked immunosorbent assay (ELISA, respectively. A histologic longitudinal analysis was performed using an AD transgenic mouse model, APP/PS1, to determine an age at which microglial protein tyrosine kinase levels increased in order to administer dasatinib via mini osmotic pump diffusion. Effects of dasatinib administration on microglial and astroglial activation, protein phosphotyrosine levels, active Src kinase levels, Aβ plaque deposition, and spatial working memory were assessed via immunohistochemistry, Western blot, and T maze analysis. Results Aβ fibrils stimulated primary murine microglia via a tyrosine kinase pathway involving Src kinase that was attenuated by dasatinib. Dasatinib administration to APP/PS1 mice decreased protein phosphotyrosine, active Src, reactive microglia, and TNFα levels in the hippocampus and temporal cortex. The drug had no effect on GFAP levels, Aβ plaque load, or the related tyrosine kinase, Lyn. These anti-inflammatory changes correlated with improved performance on the T maze test in dasatinib infused animals compared to control animals. Conclusions These data suggest that amyloid

  17. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

    Science.gov (United States)

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-01

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. DOI: http://dx.doi.org/10.7554/eLife.04494.001 PMID:25599590

  18. Hypertension in Chronic Glomerulonephritis.

    Science.gov (United States)

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  19. 72株非伤寒沙门菌药敏分析及其所致儿童肠炎的临床特点%Drug sensitivity analysis of 72 non-typhoidal Salmonella and clinical characteristics of the caused enteritis in children

    Institute of Scientific and Technical Information of China (English)

    谢广清; 龙晓玲; 梁展图; 张泉山; 付四毛

    2011-01-01

    The present paper aims to explore drug resistance of 72 non-typhoidal Salmonella isolates and the clinical characteristics of resulting enteritis in children. Stool specimens from 1 665 children experiencing intestinal infection were collected by the Digestive Disorders Ward of Zhongshan Boai Hospital from March 2009 to October 2010. The drug sensitivity testing on 72 non-typhoidal Salmonella isolates was conducted after strain identification and separation. The clinical characteristics of non-typhoidal Salmonella infection were retrospectively analyzed. The results demonstrated that sensitivities of non-typhoidal Salmonella to cefoperazone-tazobactam, Tienam, levofloxacin, piperacillin-tazobactam, and ceftazidine were 100%, 98.61%, 95.83%, 87.50% and 77.78%, respectively. Antibiotic resistance rate of these non-typhoidal Salmonella to the first and second generation cephalosporins, aminoglycosides, non-enzyme penicillin and cephamycins were all>80%. Children with intestinal infection by non-typhoidal Salmonella typically presented with clinical characteristics specific to invasive enteritis such as mucous bloody stool, omitting and fever. Older children reported more abdominal pain and showed more abdominal distension and some may deteriorate to non-typhoidal Salmonella sepsis. This study suggests that non-typhoidal Salmonella may have a high sensitivity to carbapenems, enzyme-containing β-lactam compounds, and fluoroquinolones. Therefore, antibiotics should be chosen reasonably and prudently based on drug sensitivity testing as treatment for effectively controlling infection, and preventing the occurrence of further deterioration in patients.%为探讨非伤寒沙门菌的耐药性及其引起儿童肠炎的临床特点,收集2009年3月~2010年10月广东省中山市博爱医院儿科消化病区送检的1 665例肠道感染患儿粪便标本,将培养、分离所获的72株非伤寒沙门菌进行药敏试验,并回顾分析其感染后的临床特点.结

  20. Antigen presentation by murine epidermal langerhans cells and its alteration by ultraviolet B light

    International Nuclear Information System (INIS)

    Mice that are chronically exposed in vivo to ultraviolet B light (UV-B) display altered immunologic reactivity to various antigenic stimuli. A possible mode of UV-B action is that it exerts adverse effects on antigen-presenting cell function. Because the epidermis is the only tissue that is naturally subject to UV exposure we investigated if murine epidermal cells (EC) could perform an antigen presentation function and, if so, could this function be altered by UV-B irradiation. For this purpose, T cells immune to purified protein derivative of tuberculin (PPD) and dinitrophenylated ovalbumin (DNP6-OVA) from either BALB/c or C3H/He mice were incubated with syngeneic, semisyngeneic, or allogeneic EC or, for control purposes, with peritoneal exudate cells (PEC) that had been pulse-exposed to either the immunizing antigens or, as controls, left unpulsed, or pulsed to human serum albumin (HSA). After 4 days of culture, T cell proliferation was assessed by 3H-thymidine incorporation. PPD- and DNP/6-OVA pulsed, but not HSA-pulsed EC and PEC, induced vigorous proliferation of syngeneic and semisyngeneic, but not allogeneic, immune T cells. Pretreatment of stimulator cells with specific anti-Ia serum and complement virtually abolished this response, which indicated that among EC, Ia-bearing Langerhans cells are the critical stimulators. Exposure of EC either before or after pulsing to UV-B resulted in a dose-dependent impairment of antigen-specific T cell proliferation; the T proliferative response was abolished after administration of 20 mJ/cm2 UV-B. UV-B in the dose range employed did not produce immediate lethal cell damage, premature death of cultured EC, or toxic factors inhibitory for T cell proliferation