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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. Mix-infection of S. Typhi and ParaTyphi A in Typhoid Fever and Chronic Typhoid Carriers: A Nested PCR Based Study in North India

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    Pratap, Chandra Bhan; Kumar, Gopal; Patel, Saurabh Kumar; Shukla, Vijay K; Kumar, Kailash; Singh, Tej Bali

    2014-01-01

    Introduction: Enteric fever is a systemic disease caused by Salmonella organism such as serotypes Typhi and ParaTyphi A, B, C. Salmonella ParaTyphi A contributes more than 50% of all the enteric fever cases and it has recently been projected as an emerging pathogen. Materials and Methods: The present study was aimed to detect Salmonella Typhi and ParaTyphi A in urine, blood and stool specimens collected from cases of enteric fever (110), chronic typhoid carriers (46) and healthy controls (75) to explore the possibility of mixed infection by nested PCR. A new nested PCR primer was designed targeting putative fimbrial protein (stkG) gene which is one of the fimbrial gene families to Salmonella ParaTyphi A and for S. Typhi already reported primers targeting flagellin (fliC) gene. Results: Large volume of urine specimens (15 ml) was found to be the best for detection of Salmonella serotypes. The urine sample was found to have mixed-infection by both the serotypes in 40.9% of the cases but lower in blood (27.3%) and stool (13.6%). Conclusion: The present study concludes that occurrence of mixed infection may be quite frequent in typhoid and chronic typhoid carriers’ individuals, although the reported recent rise in ParaTyphi A incidence may not be real. PMID:25584217

  4. Typhoid Vaccine

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    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, stomach ... a typhoid carrier. • Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot) • One dose provides ...

  5. Oral treatment with Saccharomyces cerevisiae strain UFMG 905 modulates immune responses and interferes with signal pathways involved in the activation of inflammation in a murine model of typhoid fever.

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    Martins, Flaviano S; Elian, Samir D A; Vieira, Angélica T; Tiago, Fabiana C P; Martins, Ariane K S; Silva, Flávia C P; Souza, Ericka L S; Sousa, Lirlândia P; Araújo, Helena R C; Pimenta, Paulo F; Bonjardim, Cláudio A; Arantes, Rosa M E; Teixeira, Mauro M; Nicoli, Jacques R

    2011-04-01

    Salmonella spp. are Gram-negative, facultative, intracellular pathogens that cause several diarrheal diseases ranging from self-limiting gastroenteritis to typhoid fever. Previous results from our laboratory showed that Saccharomyces cerevisiae strain UFMG 905 isolated from 'cachaça' production presented probiotic properties due to its ability to protect against experimental infection with Salmonella enterica serovar Typhimurium. In this study, the effects of oral treatment with S. cerevisiae 905 were evaluated at the immunological level in a murine model of typhoid fever. Treatment with S. cerevisiae 905 inhibited weight loss and increased survival rate after Salmonella challenge. Immunological data demonstrated that S. cerevisiae 905 decreased levels of proinflammatory cytokines and modulated the activation of mitogen-activated protein kinases (p38 and JNK, but not ERK1/2), NF-κB and AP-1, signaling pathways which are involved in the transcriptional activation of proinflammatory mediators. Experiments in germ-free mice revealed that probiotic effects were due, at least in part, to the binding of Salmonella to the yeast. In conclusion, S. cerevisiae 905 acts as a potential new biotherapy against S. Typhimurium infection due to its ability to bind bacteria and modulate signaling pathways involved in the activation of inflammation in a murine model of typhoid fever.

  6. 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, e...

  7. Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.

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    Jiseon Yang

    2015-06-01

    Full Text Available A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 10(5 CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

  8. Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.

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    Yang, Jiseon; Barrila, Jennifer; Roland, Kenneth L; Kilbourne, Jacquelyn; Ott, C Mark; Forsyth, Rebecca J; Nickerson, Cheryl A

    2015-06-01

    A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 10(5) CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

  9. Neurological Disorders in a Murine Model of Chronic Renal Failure

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    Jean-Marc Chillon

    2014-01-01

    Full Text Available Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF. However, data on the impact of CRF on the cerebral circulatory system are scarce—despite the fact that stroke is the third most common cause of cardiovascular death in people with CRF. In the present study, we examined the impact of CRF on behavior (anxiety, recognition and ischemic stroke severity in a well-defined murine model of CRF. We did not observe any significant increases between CRF mice and non-CRF mice in terms of anxiety. In contrast, CRF mice showed lower levels of anxiety in some tests. Recognition was not impaired (vs. controls after 6 weeks of CRF but was impaired after 10 weeks of CRF. Chronic renal failure enhances the severity of ischemic stroke, as evaluated by the infarct volume size in CRF mice after 34 weeks of CRF. Furthermore, neurological test results in non-CRF mice tended to improve in the days following ischemic stroke, whereas the results in CRF mice tended to worsen. In conclusion, we showed that a murine model of CRF is suitable for evaluating uremic toxicity and the associated neurological disorders. Our data confirm the role of uremic toxicity in the genesis of neurological abnormalities (other than anxiety.

  10. Haematological Alterations Due to Typhoid Fever in Enugu Urban- Nigeria

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    Okafor, A. I.

    2007-01-01

    Full Text Available Some specific haematological changes that accompany chronic and severe typhoid fever were investigated in an endemic area of Enugu Urban-Nigeria. The results established that typhoid fever infections led to a statistically significant leucopenia (p < 0.05. In acute, chronic cases, leucopenia is accompanied with significant oligocythaemia, thrombocytopenia, anaemia and lowered haematocrit (p < 0.05. The importance of the results in the diagnosis and treatment of typhoid fever are discussed.

  11. Studies to Control Endemic Typhoid Fever in Chile

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    1986-09-01

    Screening Test for Chronic Typhoid Carriers Tyraminated Vi pol1yc iride was used as antigen in an ELISA to detect Vi antibody. IgG class Vi antibodies were...from foodhandlers from the indigenous popilation who way be chronic typhoid carriers and who unknowingly are involved in preparation of food . Under...these circumstances, unwittingly, the potential exists for large epidamics to 2 occur. Furthesmore, the size of the irocla of S. typ4 present in food

  12. 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.

  13. A novel inexpensive murine model of oral chronic digitalization.

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    Helber, Izo; Kanashiro, Rosemeire M; Alarcon, Ernesto A; Antonio, Ednei L; Tucci, Paulo J F

    2004-01-01

    A novel inexpensive murine model of oral administration of digitoxin (100 micro g/kg per day) added to routine chow is described. Serum digitoxin levels achieved after oral (n = 5; 116 +/- 14 ng/mL) and subcutaneous (n = 5; 124 +/- 11 ng/mL) administration were similar. A significant increase in the maximal left ventricular pressure rise of treated (n = 9) compared with control (n = 6) rats (dP/dt: 8956 +/- 233 vs 7980 +/- 234 mmHg/s, respectively; P = 0.01) characterized the positive inotropic action of digitoxin. In addition, no differences were observed in treated compared with control rats with regard to the electrocardiogram and systolic and diastolic left ventricular pressures.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Novel Structure and Function of Typhoid Toxin

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    ... Matters NIH Research Matters July 29, 2013 Novel Structure and Function of Typhoid Toxin Structure of typhoid toxin, showing the 2 A subunits ( ... to cultured cells. The scientists next determined the structure of the typhoid toxin. The toxin was already ...

  19. Chronic murine toxoplasmosis is defined by subtle changes in neuronal connectivity

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    Alexandru Parlog

    2014-04-01

    Full Text Available Recent studies correlate chronic Toxoplasma gondii (T. gondii infection with behavioral changes in rodents; additionally, seropositivity in humans is reported to be associated with behavioral and neuropsychiatric diseases. In this study we investigated whether the described behavioral changes in a murine model of chronic toxoplasmosis are associated with changes in synaptic plasticity and brain neuronal circuitry. In mice chronically infected with T. gondii, magnetic resonance imaging (MRI data analysis displayed the presence of heterogeneous lesions scattered throughout all brain areas. However, a higher density of lesions was observed within specific regions such as the somatosensory cortex (SSC. Further histopathological examination of these brain areas indicated the presence of activated resident glia and recruited immune cells accompanied by limited alterations of neuronal viability. In vivo diffusion-tensor MRI analysis of neuronal fiber density within the infected regions revealed connectivity abnormalities in the SSC. Altered fiber density was confirmed by morphological analysis of individual, pyramidal and granule neurons, showing a reduction in dendritic arbor and spine density within the SSC, as well as in the hippocampus. Evaluation of synapse efficacy revealed diminished levels of two key synaptic proteins, PSD95 and synaptophysin, within the same brain areas, indicating deficits in functionality of the synaptic neurotransmission in infected mice. Our results demonstrate that persistent T. gondii infection in a murine model results in synaptic deficits within brain structures leading to disturbances in the morphology of noninfected neurons and modified brain connectivity, suggesting a potential explanation for the behavioral and neuropsychiatric alterations.

  20. Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin.

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    Peggy S Lai

    Full Text Available RATIONALE: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD. These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. METHODS: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. RESULTS: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. CONCLUSIONS: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene

  1. 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.

  2. Ciprofloxacin resistant osteomyelitis following typhoid fever

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    Ayeni, Itunuayo V; Calver, Graeme

    2012-01-01

    Salmonella typi is a rare cause of chronic osteomyelitis in a non-sickle cell patient. The authors report the case of a 25-year-old gentleman with a history of typhoid fever and an infected skin nodule on his left forearm 5 years prior to the diagnosis. He was referred to our orthopaedic colleagues with chronic osteomyelitis and underwent debridement of the bone for which samples grew Salmonella typhi. He was commenced on intravenous ceftriaxone 2 g once daily for 6 weeks followed by oral azi...

  3. 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.

  4. Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma.

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    Nader, Manar A

    2015-12-01

    In this study the role of sitagliptin, dipeptidyl peptidase inhibitor, DPP-4, and dexamethasone in ameliorating inflammation and remodeling of chronic asthma in a mouse model were investigated. Mice sensitized to ovalbumin were chronically challenged with aerosolized antigen for 3days a week continued for 8weeks. During this period animals were treated with sitagliptin or dexamethasone daily. Assessment of inflammatory cell, oxidative markers, total nitrate/nitrite (NOx), interleukin (IL)-13, transforming growth factor-beta1 (TGF-β1) in bronchoalveolar lavage (BAL) and/or lung tissue were done. Also histopathological and immuno-histochemical analysis for lung was carried out. Compared with vehicle alone, treatment with sitagliptin or dexamethasone significantly reduced accumulation of eosinophils and chronic inflammatory cells, subepithelial collagenization, and thickening of the airway epithelium. Also both drug reduced goblet cell hyperplasia, oxidative stress, TGF-β1, IL-13 and epithelial cytoplasmic immunoreactivity for nuclear factor κ-B (NFκ-B). These data indicate that sitagliptin like dexamethasone may play a beneficial role reducing airway inflammation and remodeling in chronic murine model of asthma.

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

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    Del Bel Belluz, Lisa; Guidi, Riccardo; Pateras, Ioannis S.

    2016-01-01

    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...... 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...

  6. Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic allergic contact dermatitis.

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    Tamaka, Kyoko; Seike, Masahiro; Hagiwara, Tamio; Sato, Atsushi; Ohtsu, Hiroshi

    2015-04-01

    Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (-/-) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6-trinitro-1-chlorobenzene (TNCB) on HDC (+/+) and HDC (-/-) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF-β1 in this model. Recombinant TGF-β1 or anti-TGF-β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine-regulated TGF-β on the Treg population in CACD. Recombinant TGF-β1 injection promoted the infiltration of Tregs in the skin and the production of IL-10; however, anti-TGF-β1 antibody injection suppressed the number of Tregs in the skin and the production of IL-10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF-β.

  7. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

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    Scott W Cousins

    Full Text Available The neovascular (wet form of age-related macular degeneration (AMD leads to vision loss due to choroidal neovascularization (CNV. Since macrophages are important in CNV development, and cytomegalovirus (CMV-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV, laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF, an outcome that requires active virus replication.

  8. A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis.

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    Ferguson, Polly J; Bing, Xinyu; Vasef, Mohammed A; Ochoa, Luis A; Mahgoub, Amar; Waldschmidt, Thomas J; Tygrett, Lorraine T; Schlueter, Annette J; El-Shanti, Hatem

    2006-01-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder that primarily affects bone but is often accompanied by inflammation of the skin and/or gastrointestinal tract. The etiology is unknown but evidence suggests a genetic component to disease susceptibility. Although most cases of CRMO are sporadic, there is an autosomal recessive syndromic form of the disease, called Majeed syndrome, which is due to homozygous mutations in LPIN2. In addition, there is a phenotypically similar mouse, called cmo (chronic multifocal osteomyelitis) in which the disease is inherited as an autosomal recessive disorder. The cmo locus has been mapped to murine chromosome 18. In this report, we describe phenotypic abnormalities in the cmo mouse that include bone, cartilage and skin inflammation. Utilizing a backcross breeding strategy, we refined the cmo locus to a 1.3 Mb region on murine chromosome 18. Within the refined region was the gene pstpip2, which shares significant sequence homology to the PSTPIP1. Mutations in PSTPIP1 have been shown to cause the autoinflammatory disorder PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne). Mutation analysis, utilizing direct sequencing, revealed a single base pair change c.293T --> C in the pstpip2 gene resulting in a highly conserved leucine at amino acid 98 being replaced by a proline (L98P). No other mutations were found in the coding sequence of the remaining genes in the refined interval, although a 50 kb gap remains unexplored. These data suggest that mutations in pstpip2 may be the genetic explanation for the autoinflammatory phenotype seen in the cmo mouse.

  9. 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.

  10. Ciprofloxacin resistant osteomyelitis following typhoid fever.

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    Ayeni, Itunuayo V; Calver, Graeme

    2012-07-13

    Salmonella typi is a rare cause of chronic osteomyelitis in a non-sickle cell patient. The authors report the case of a 25-year-old gentleman with a history of typhoid fever and an infected skin nodule on his left forearm 5 years prior to the diagnosis. He was referred to our orthopaedic colleagues with chronic osteomyelitis and underwent debridement of the bone for which samples grew Salmonella typhi. He was commenced on intravenous ceftriaxone 2 g once daily for 6 weeks followed by oral azithromycin 500 mg once daily for a further 6 weeks. The purpose of this case report is to consider the possible mode for antibiotic resistance. In this patient, the authors believe that partial treatment of the typhoid fever 5 years prior to diagnosis of osteomyelitis enabled antibiotic resistance to ciprofloxacin. Furthermore, the authors believe that the infected nodule was the result of direct inoculation with the Salmonella organism which then acted as a focus for further infections.

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

    Science.gov (United States)

    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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Xenotropic Murine Leukemia Virus-Related Virus in Monozygotic Twins Discordant for Chronic Fatigue Syndrome

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    Jerome, Keith R.; Diem, Kurt; Huang, Meei-Li; Selke, Stacy; Corey, Lawrence; Buchwald, Dedra

    2011-01-01

    A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV, and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored PBMC were tested with 3 separate PCR assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins were positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a followup plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS. PMID:21795004

  17. Typhoidal and non-typhoidal Salmonella infections in Africa.

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    Smith, S I; Seriki, A; Ajayi, A

    2016-12-01

    Salmonella infections in humans can range from self-limiting gastroenteritis typically associated with non-typhoidal Salmonella (NTS) to typhoidal fever, which can be life-threatening. Salmonellosis causes considerable morbidity and mortality in both humans and animals, and has a significant socioeconomic impact worldwide. In Africa, it is difficult to evaluate the situation of salmonellosis due to the non-availability of facilities capable of performing the tests essential for the diagnosis of typhoidal and non-typhoidal Salmonella infections. This article reviews important work in the literature, including the epidemiology, disease burden, pathogenesis, genomics, diagnosis, treatment, emergence and tracking of multidrug-resistant (MDR) Salmonella infections and intercontinental transmission of Salmonella to Africa. Searches of PubMed and Google Scholar were completed and the retrieved list of relevant publications were further screened. The literature revealed that the most common form of the disease in Africa is gastroenteritis, with bacterial multiplication in intestinal submucosa and diarrhoea caused by the inflammatory response and, perhaps, also by toxins. In addition to the high burden of Salmonella infection in Africa, MDR Salmonella species is on the rise in the continent, which might pose difficulties in the treatment of the disease.

  18. Radiological observation in typhoid fever

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    Lim, K. Y.; Park, H. Y.; Kim, J. D.; Rhee, H. S. [Presbyterian Medical Center, Jeonju (Korea, Republic of)

    1985-12-15

    Radiographic findings in plain abdominal films, chest PA and liver scanning are considered to be ancillary diagnostic methods for uncomplicated typhoid fever and a valuable method for detection of complication such as intestinal perforation. 189 cases of clinically proven typhoid fever from Mar. 1973 to Feb. 1979 in this Hospital were reviewed and radiographic findings were analyzed carefully. The results are as follows: 1. Most (73.6%) cases were between 20 and 40 years of age. 2. Three of the most common radiographic findings were as follows: 1) Localized paralytic ileus in RLQ or diffuse paralytic ileus (96.3%). 2) Hepatomegaly (56.5%). 3) Splenomegaly (49.7%). 3. In cases of typhoid fever with intestinal perforation there were additional significant findings such as free air under diaphragm (85%), free fluid in peritoneal cavity (90%) and air fluid levels in RLQ (80%). 4. The most frequent chest x-ray finding was elevation of diaphragm (11.1%). 5. 8 cases of complicated typhoid fever which eventually came to operation were diagnosed only by radiographic method.

  19. Antimicrobial resistance in typhoidal salmonellae

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    B N Harish

    2011-01-01

    Full Text Available Infections with Salmonella are an important public health problem worldwide. On a global scale, it has been appraised that Salmonella is responsible for an estimated 3 billion human infections each year. The World Health Organization (WHO has estimated that annually typhoid fever accounts for 21.7 million illnesses (217,000 deaths and paratyphoid fever accounts for 5.4 million of these cases. Infants, children, and adolescents in south-central and South-eastern Asia experience the greatest burden of illness. In cases of enteric fever, including infections with S. Typhi and S. Paratyphi A and B, it is often necessary to commence treatment before the results of laboratory sensitivity tests are available. Hence, it is important to be aware of options and possible problems before beginning treatment. Ciprofloxacin has become the first-line drug of choice since the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin, and trimethoprim. There is increase in the occurrence of strains resistant to ciprofloxacin. Reports of typhoidal salmonellae with increasing minimum inhibitory concentration (MIC and resistance to newer quinolones raise the fear of potential treatment failures and necessitate the need for new, alternative antimicrobials. Extended-spectrum cephalosporins and azithromycin are the options available for the treatment of enteric fever. The emergence of broad spectrum β-lactamases in typhoidal salmonellae constitutes a new challenge. Already there are rare reports of azithromycin resistance in typhoidal salmonellae leading to treatment failure. This review is based on published research from our centre and literature from elsewhere in the world. This brief review tries to summarize the history and recent trends in antimicrobial resistance in typhoidal salmonellae.

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

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    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.

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

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    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

  2. Murine Models for Trypanosoma brucei gambiense disease progression--from silent to chronic infections and early brain tropism.

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    Christiane Giroud

    Full Text Available Human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates.T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS, a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms

  3. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

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    Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

    2017-01-01

    Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

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

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    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.

  5. 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.

  6. Searching for the elusive typhoid diagnostic

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    Baker Stephen

    2010-03-01

    Full Text Available Abstract Typhoid (enteric fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area.

  7. Abdominal ultrasonographic findings in typhoid fever: a comparison between typhoid patients and those with non-typhoidal Salmonella and Campylobacter jejuni enterocolitis.

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    Kobayashi, Akira; Adachi, Yasuo; Iwata, Yoshinori; Sakai, Yoshiyuki; Shigemitu, Kazuaki; Todoroki, Miwako; Ide, Mituru

    2012-03-01

    Typhoid fever is a major health problem in many developing countries and its clinical features are similar to other types of bacterial enterocolitis. Definitive diagnosis by blood culture requires several days and is often unfeasible to perform in developing countries. More efficient and rapid diagnostic methods for typhoid are needed. We compared the pathological changes in the bowel and adjacent tissues of patients having typhoid fever with those having bacterial enterocolitis using ultrasonography. A characteristic of patients with non-typhoidal Salmonella and Campylobacter jejuni enterocolitis was mural thickening of the terminal ileum; only mild mural swelling or no swelling was observed in patients with typhoid fever. Mesenteric lymph nodes in patients with typhoid fever were significantly more enlarged compared to patients with other types of bacterial enterocolitis. Our findings suggest typhoid fever is not fundamentally an enteric disease but rather resembles mesenteric lymphadenopathy and ultrasound is a promising modality for diagnosing typhoid fever in developing countries.

  8. The combination of Bifidobacterium breve with non-digestible oligosaccharides suppresses airway inflammation in a murine model for chronic asthma.

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    Sagar, Seil; Vos, Arjan P; Morgan, Mary E; Garssen, Johan; Georgiou, Niki A; Boon, Louis; Kraneveld, Aletta D; Folkerts, Gert

    2014-04-01

    Over the last decade, there has been a growing interest in the use of interventions that target the intestinal microbiota as a treatment approach for asthma. This study is aimed at exploring the therapeutic effects of long-term treatment with a combination of Bifidobacterium breve with non-digestible oligosaccharides on airway inflammation and remodeling. A murine ovalbumin-induced chronic asthma model was used. Pulmonary airway inflammation; mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in vitro T cell activation; mast cell degranulation; and airway remodeling were examined. The combination of B. breve with non-digestible oligosaccharides suppressed pulmonary airway inflammation; reduced T cell activation and mast cell degranulation; modulated expression of pattern recognition receptors, cytokines and transcription factors; and reduced airway remodeling. The treatment induced regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T cells. This specific combination of beneficial bacteria with non-digestible oligosaccharides has strong anti-inflammatory properties, possibly via the induction of a regulatory T cell response, resulting in reduced airway remodeling and, therefore, may be beneficial in the treatment of chronic inflammation in allergic asthma.

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

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    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.

  10. Chronic liver inflammation modifies DNA methylation at the precancerous stage of murine hepatocarcinogenesis.

    Science.gov (United States)

    Stoyanov, Evgeniy; Ludwig, Guy; Mizrahi, Lina; Olam, Devorah; Schnitzer-Perlman, Temima; Tasika, Elena; Sass, Gabriele; Tiegs, Gisa; Jiang, Yong; Nie, Ting; Kohler, James; Schinazi, Raymond F; Vertino, Paula M; Cedar, Howard; Galun, Eithan; Goldenberg, Daniel

    2015-05-10

    Chronic liver inflammation precedes the majority of hepatocellular carcinomas (HCC). Here, we explore the connection between chronic inflammation and DNA methylation in the liver at the late precancerous stages of HCC development in Mdr2(-/-) (Mdr2/Abcb4-knockout) mice, a model of inflammation-mediated HCC. Using methylated DNA immunoprecipitation followed by hybridization with "CpG islands" (CGIs) microarrays, we found specific CGIs in 76 genes which were hypermethylated in the Mdr2(-/-) liver compared to age-matched healthy controls. The observed hypermethylation resulted mainly from an age-dependent decrease of methylation of the specific CGIs in control livers with no decrease in mutant mice. Chronic inflammation did not change global levels of DNA methylation in Mdr2(-/-) liver, but caused a 2-fold decrease of the global 5-hydroxymethylcytosine level in mutants compared to controls. Liver cell fractionation revealed, that the relative hypermethylation of specific CGIs in Mdr2(-/-) livers affected either hepatocyte, or non-hepatocyte, or both fractions without a correlation between changes of gene methylation and expression. Our findings demonstrate that chronic liver inflammation causes hypermethylation of specific CGIs, which may affect both hepatocytes and non-hepatocyte liver cells. These changes may serve as useful markers of an increased regenerative activity and of a late precancerous stage in the chronically inflamed liver.

  11. The MET Receptor Tyrosine Kinase Confers Repair of Murine Pancreatic Acinar Cells following Acute and Chronic Injury

    Science.gov (United States)

    Gaziova, Ivana; Jackson, Daniel; Boor, Paul J.; Carter, Dwayne; Cruz-Monserrate, Zobeida; Elferink, Cornelis J.; Joshi, Aditya D.; Kaphalia, Bhupendra; Logsdon, Craig D.; Pereira de Castro, Karen; Soong, Lynn; Tao, Xinrong; Qiu, Suimin; Elferink, Lisa A.

    2016-01-01

    Acinar cells represent the primary target in necroinflammatory diseases of the pancreas, including pancreatitis. The signaling pathways guiding acinar cell repair and regeneration following injury remain poorly understood. The purpose of this study was to determine the importance of Hepatocyte Growth Factor Receptor/MET signaling as an intrinsic repair mechanism for acinar cells following acute damage and chronic alcohol-associated injury. Here, we generated mice with targeted deletion of MET in adult acinar cells (MET-/-). Acute and repetitive pancreatic injury was induced in MET-/- and control mice with cerulein, and chronic injury by feeding mice Lieber-DeCarli diets containing alcohol with or without enhancement of repetitive pancreatic injury. We examined the exocrine pancreas of these mice histologically for acinar death, edema, inflammation and collagen deposition and changes in the transcriptional program. We show that MET expression is relatively low in normal adult pancreas. However, MET levels were elevated in ductal and acinar cells in human pancreatitis specimens, consistent with a role for MET in an adaptive repair mechanism. We report that genetic deletion of MET in adult murine acinar cells was linked to increased acinar cell death, chronic inflammation and delayed recovery (regeneration) of pancreatic exocrine tissue. Notably, increased pancreatic collagen deposition was detected in MET knockout mice following repetitive injury as well alcohol-associated injury. Finally, we identified specific alterations of the pancreatic transcriptome associated with MET signaling during injury, involved in tissue repair, inflammation and endoplasmic reticulum stress. Together, these data demonstrate the importance of MET signaling for acinar repair and regeneration, a novel finding that could attenuate the symptomology of pancreatic injury. PMID:27798657

  12. Typhoid fever in Fiji: a reversible plague?

    Science.gov (United States)

    Thompson, Corinne N; Kama, Mike; Acharya, Shrish; Bera, Una; Clemens, John; Crump, John A; Dawainavesi, Aggie; Dougan, Gordon; Edmunds, W John; Fox, Kimberley; Jenkins, Kylie; Khan, M Imran; Koroivueta, Josefa; Levine, Myron M; Martin, Laura B; Nilles, Eric; Pitzer, Virginia E; Singh, Shalini; Raiwalu, Ratu Vereniki; Baker, Stephen; Mulholland, Kim

    2014-10-01

    The country of Fiji, with a population of approximately 870 000 people, faces a growing burden of several communicable diseases including the bacterial infection typhoid fever. Surveillance data suggest that typhoid has become increasingly common in rural areas of Fiji and is more frequent amongst young adults. Transmission of the organisms that cause typhoid is facilitated by faecal contamination of food or water and may be influenced by local behavioural practices in Fiji. The Fijian Ministry of Health, with support from Australian Aid, hosted a meeting in August 2012 to develop comprehensive control and prevention strategies for typhoid fever in Fiji. International and local specialists were invited to share relevant data and discuss typhoid control options. The resultant recommendations focused on generating a clearer sense of the epidemiology of typhoid in Fiji and exploring the contribution of potential transmission pathways. Additionally, the panel suggested steps such as ensuring that recommended ciprofloxacin doses are appropriate to reduce the potential for relapse and reinfection in clinical cases, encouraging proper hand hygiene of food and drink handlers, working with water and sanitation agencies to review current sanitation practices and considering a vaccination policy targeting epidemiologically relevant populations.

  13. 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

  14. 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.

  15. Delayed bone regeneration is linked to chronic inflammation in murine muscular dystrophy.

    Science.gov (United States)

    Abou-Khalil, Rana; Yang, Frank; Mortreux, Marie; Lieu, Shirley; Yu, Yan-Yiu; Wurmser, Maud; Pereira, Catia; Relaix, Frédéric; Miclau, Theodore; Marcucio, Ralph S; Colnot, Céline

    2014-02-01

    Duchenne muscular dystrophy (DMD) patients exhibit skeletal muscle weakness with continuous cycles of muscle fiber degeneration/regeneration, chronic inflammation, low bone mineral density, and increased risks of fracture. Fragility fractures and associated complications are considered as a consequence of the osteoporotic condition in these patients. Here, we aimed to establish the relationship between muscular dystrophy and fracture healing by assessing bone regeneration in mdx mice, a model of DMD with absence of osteoporosis. Our results illustrate that muscle defects in mdx mice impact the process of bone regeneration at various levels. In mdx fracture calluses, both cartilage and bone deposition were delayed followed by a delay in cartilage and bone remodeling. Vascularization of mdx fracture calluses was also decreased during the early stages of repair. Dystrophic muscles are known to contain elevated numbers of macrophages contributing to muscle degeneration. Accordingly, we observed increased macrophage recruitment in the mdx fracture calluses and abnormal macrophage accumulation throughout the process of bone regeneration. These changes in the inflammatory environment subsequently had an impact on the recruitment of osteoclasts and the remodeling phase of repair. Further damage to the mdx muscles, using a novel model of muscle trauma, amplified both the chronic inflammatory response and the delay in bone regeneration. In addition, PLX3397 treatment of mdx mice, a cFMS (colony stimulating factor receptor 1) inhibitor in monocytes, partially rescued the bone repair defect through increasing cartilage deposition and decreasing the number of macrophages. In conclusion, chronic inflammation in mdx mice contributes to the fracture healing delay and is associated with a decrease in angiogenesis and a transient delay in osteoclast recruitment. By revealing the role of dystrophic muscle in regulating the inflammatory response during bone repair, our results

  16. Microscopic haematuria: A rare presentation of typhoid fever.

    Science.gov (United States)

    Nisahan, Balasingam; Thirunavukarasu, Kumanan; Selvaratnam, Gowry

    2015-04-01

    Typhoid fever can cause a number of renal manifestations heretofore dubbed 'nephrotyphoid'. Haematuria in the absence of renal impairment is extremely rare among typhoid patients. We report a case of an adult who presented with a prolonged febrile illness and microscopic haematuria. Blood culture confirmed the diagnosis of typhoid and the patient was treated successfully with ceftriaxone.

  17. Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Thomas eQuinn

    2011-08-01

    Full Text Available Multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including the optic nerve. Neuronal and axonal damage is considered to be the main cause of long-term disability in patients with MS. Neuronal loss, including retinal ganglion cell (RGC apoptosis in eyes with optic neuritis, also occurs in EAE. However, there is significant variability in the clinical course and level of neuronal damage in MS and EAE. The current studies examine the mechanisms and kinetics of RGC loss in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein to induce a chronic EAE disease. Clinical progression of EAE was scored daily and vision was assessed by optokinetic responses. At various time points, RGCs were counted and optic nerves were examined for inflammatory cell infiltration. Almost all EAE mice develop optic neuritis by day 15 post-immunization; however, RGC loss is delayed in these mice. No RGC loss is detected 25 days post-immunization, whereas RGC numbers in EAE mice significantly and progressively decrease compared to controls from 35-50 days post-immunization. The delayed time course of RGC loss is in stark contrast to that reported in relapsing EAE, as well as in rats with chronic EAE. Results suggest that different clinical disease courses of optic nerve inflammation may trigger distinct mechanisms of neuronal damage, or RGCs in different rodent strains may have variable resistance to neuronal degeneration.

  18. MALARIA TYPHOID CO - INFECTION AMONG FEBRILE PATIENTS

    Directory of Open Access Journals (Sweden)

    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.

  19. Typhoid fever: case report and literature review.

    Science.gov (United States)

    Sanhueza Palma, Natalia Carolina; Farías Molina, Solange; Calzadilla Riveras, Jeannette; Hermoso, Amalia

    2016-06-21

    Typhoid fever remains a major health problem worldwide, in contrast to Chile, where this disease is an isolated finding. Clinical presentation is varied, mainly presenting with fever, malaise, abdominal discomfort, and nonspecific symptoms often confused with other causes of febrile syndrome. We report a six-year-old, male patient presenting with fever of two weeks associated with gastrointestinal symptoms, malaise, hepatomegaly and elevated liver enzymes. Differential diagnoses were considered and a Widal reaction and two blood cultures were requested; both came back positive, confirming the diagnosis of typhoid fever caused by Salmonella typhi. Prior to diagnosis confirmation, empirical treatment was initiated with ceftriaxone and metronidazole, with partial response; then drug therapy was adjusted according to ciprofloxacin susceptibility testing with a favorable clinical response. We discuss diagnostic methods and treatment of enteric fever with special emphasis on typhoid fever.

  20. 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.

  1. 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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Typhoid toxin provides a window into typhoid fever and the biology of Salmonella Typhi.

    Science.gov (United States)

    Galán, Jorge E

    2016-06-07

    Salmonella Typhi is the cause of typhoid fever, a disease that has challenged humans throughout history and continues to be a major public health concern. Unlike infections with most other Salmonellae, which result in self-limiting gastroenteritis, typhoid fever is a life-threatening systemic disease. Furthermore, in contrast to most Salmonellae, which can infect a broad range of hosts, S. Typhi is a strict human pathogen. The unique features of S. Typhi pathogenesis and its stringent host specificity have been a long-standing puzzle. The discovery of typhoid toxin not only has provided major insight into these questions but also has offered unique opportunities to develop novel therapeutic and prevention strategies to combat typhoid fever.

  5. Vi serology in screening of typhoid carriers: improved specificity by detection of Vi antibodies by counterimmunoelectrophoresis.

    OpenAIRE

    Chau, P. Y.; Tsang, R S

    1982-01-01

    A purified soluble Vi antigen was used in counterimmunoelectrophoresis (CIE), passive haemagglutination (HA) and solid phase radio-immunoassay (SPRIA) for detection of serum Vi antibody. Serum Vi antibody was detected in 13 of 14 chronic typhoid carriers by both CIE and HA. SPRIA studies showed that Vi antibodies in sera of these carriers were mainly of the IgG class. Successful treatment with amoxycillin in one carrier, who initially showed a positive Vi test, resulted in a reversion in 6 mo...

  6. 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.

  7. 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.

  8. Host-pathogen interactions in typhoid fever

    NARCIS (Netherlands)

    de Jong, H.K.

    2015-01-01

    This thesis focuses on host-pathogen interactions in Salmonella Typhi and Burkholderia pseudomallei infections and explores the interplay between these bacteria and the innate immune system. Typhoid fever is one of the most common causes of bacterial infection in low-income countries. With adequate

  9. 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...

  10. Typhoid perforation of small bowel: a study of 72 cases.

    Science.gov (United States)

    Noorani, M A; Sial, I; Mal, V

    1997-08-01

    Typhoid perforation, a serious complication of typhoid fever, is still common in Third World countries and has a mortality rate between 1 and 39.3% according to various reports. There are different approaches to the treatment of typhoid perforation. Early surgical intervention with simple closure of the perforation in two layers has good results and negligible mortality. It is easy to perform and can be carried out, even by a trainee surgeon.

  11. Surgical complications of typhoid fever: enteric perforation.

    Science.gov (United States)

    Santillana, M

    1991-01-01

    Typhoid fever remains a prevalent disease in developing nations as the result of adverse socioeconomic factors. The most frequent complication, and principal cause of mortality, is perforation of the terminal ileum. This report presents our experience with 96 patients surgically treated at Cayetano Heredia University Hospital in Lima, Peru from 1972 to 1986. The clinical characteristics and the diverse surgical procedures utilized in the management of these patients are reviewed.

  12. Typhoid ileal perforation: a 13-year experience

    Directory of Open Access Journals (Sweden)

    Poras Chaudhary

    2015-07-01

    Full Text Available Typhoid fever is endemic in many developing countries with a high rate of complications. Aim of this study is to analyse epidemiological features, clinical presentations, complications and therapeutic outcomes of enteric perforation peritonitis diagnosed and treated in our hospital. Records of total number of 646 patients, who presented with perforation peritonitis due to enteric fever in the surgical emergency unit of Dr Ram Manohar Lohia hospital, New Delhi between January 2001 and December 2013, were reviewed retrospectively. Descriptive statistics was used to analyze the data. Out of 646 patients, 62 (9.59% presented in shock. Stomal, peristomal, local and systemic complications were high in these patients. Primary closure was done in 212 (33.12 patients, primary ileostomy was created in 410 (64.06 patients, and resection and anastomosis was done in 24 (3.75 patients. Thirteen patients (2.01% died of typhoid intestinal perforation. To prevent complications of typhoid fever, in addition to control sanitation, it is also important to control quackery and malpractices. Awareness and education about the disease, its nature and complications will also be of great help.

  13. Splenic abscess in typhoid fever -Surgical management

    Institute of Scientific and Technical Information of China (English)

    Col Prasan Kumar Hota

    2009-01-01

    Splenic abscess is an uncommon clinical presentation in surgical practice,associated with high morbidity and mortality.Mortality may be 100 % if left untreated.Splenic abscess is also rarely encountered as a complica-tion of typhoid fever.We present here a case of multiple splenic abscesses with neuropsychiatric complications due to typhoid fever,which was managed successfully with splenectomy and other supportive therapies.Anoth-er case of single splenic abscess due to enteric fever was treated successfully with CT-guided aspiration and ap-propriate antibiotics.Being a rare entity in clinical practice,splenic abscess has been poorly studied.Haemat-ogenous seeding of the spleen due to typhoid is a common cause of splenic abscess in the tropical countries.In multiple or multiloculated abscesses aspiration usually does not succeed,which happened in our case.Sple-nectomy remains the definitive choice of treatment.However,Ultra sonography (USG)or CT-guided aspira-tion may be tried in selective cases.

  14. Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor

    Institute of Scientific and Technical Information of China (English)

    ZHU Tao; ZHANG Wei; WANG Dao-xin; HUANG Ni-wen; BO Hong; DENG Wang; DENG Jia

    2012-01-01

    Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction,pulmonary inflammation and airway remodeling.Current standard therapies for asthma provide symptomatic control,but fail to target the underlying disease pathology.Furthermore,no therapeutic agent is effective in preventing airway remodeling.A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity.In this study,we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma.Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma.The recruitment of inflammatory cells into bronchoalveolar lavage fluid (BALF) and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining.ELISA was used for measuring the levels of IL-4,IL-5,IL-13 and TNF-α in BALF.Periodic acid-Schiff (PAS) staining was used for mucus secretion.Gamma-aminobutyric acid type A receptor (GABAAR)32 expression was measured by means of immunohistochemistry,reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results Rosuvastatin reduced the number of total inflammatory cells,lymphocytes,macrophages,neutrophils,and eosinophils recruited into BALF,the levels of IL-4,IL-5,IL-13 and TNF-α in BALF,along with the histological mucus index (HMI) and GABAAR β2 expression.Changes occurred in a dose-dependent manner.Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma,rosuvastatin may be a useful therapeutic agent for treatment of asthma.

  15. Burden of typhoid fever in Sulaimania, Iraqi Kurdistan

    Directory of Open Access Journals (Sweden)

    Jonathan Dworkin

    2014-10-01

    Discussion: Cost-effective surveillance projects to calculate disease burden of typhoid fever are practical and replicable. Typhoid has successfully adapted to the healthcare environment in Sulaimania. Additional work in the region should focus on antibiotic resistance and other enteric pathogens such as Brucella spp.

  16. Acute transverse myelitis: an unusual complication of typhoid fever.

    Science.gov (United States)

    Mishra, Kirtisudha; Kaur, Sharandeep; Basu, Srikanta; Gulati, Praveen; Parakh, Ankit

    2012-08-01

    Typhoid fever is associated with a wide spectrum of neurological complications. Acute transverse myelitis is a rare complication with only a few reports in adults and none in children. A 15-year-old boy with typhoid fever is reported who developed acute transverse myelitis in the 3rd week of illness. He was treated with antibiotics and corticosteroids and made a complete recovery.

  17. Risk factors for typhoid and paratyphoid fever in Jakarta, Indonesia

    NARCIS (Netherlands)

    Vollaard, A.M.; Ali, S.; Asten, H.A.G.H. van; Widjaja, S.; Visser, L.G.; Surjadi, C.; Dissel, J.T. van

    2004-01-01

    CONTEXT: The proportion of paratyphoid fever cases to typhoid fever cases may change due to urbanization and increased dependency on food purchased from street vendors. For containment of paratyphoid a different strategy may be needed than for typhoid, because risk factors for disease may not coinci

  18. Typhoid fever in a South African in-patient population

    NARCIS (Netherlands)

    Khan, Mohammad Enayet Hossain

    2004-01-01

    In conclusion, the data presented herein show that no single clinical or paraclinical parameter is reliable in arriving at a correct clinical diagnosis of typhoid fever and that bacteriologic confirmation is necessary for the diagnosis of typhoid fever. Patients ’ age and sex influence the clinical

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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    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

  5. 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.

  6. [Conjugate vaccines against bacterial infections: typhoid fever].

    Science.gov (United States)

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J

    1992-01-01

    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  7. 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

  8. Typhoid fever acquired in the United States, 1999-2010: epidemiology, microbiology, and use of a space-time scan statistic for outbreak detection.

    Science.gov (United States)

    Imanishi, M; Newton, A E; Vieira, A R; Gonzalez-Aviles, G; Kendall Scott, M E; Manikonda, K; Maxwell, T N; Halpin, J L; Freeman, M M; Medalla, F; Ayers, T L; Derado, G; Mahon, B E; Mintz, E D

    2015-08-01

    Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space-time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space-time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space-time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

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

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    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.

  10. 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.

  11. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model

    OpenAIRE

    Pilat, Nina; Farkas, Andreas M.; Mahr, Benedikt; Schwarz, Christoph; Unger, Lukas; Hock, Karin; Oberhuber, Rupert; Aumayr, Klaus; Wrba, Fritz; Wekerle, Thomas

    2014-01-01

    Background The mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection. Metho...

  12. Typhoid fever with caecal ulcer bleed: managed conservatively.

    Science.gov (United States)

    Boopathy, Vinoth; Periyasamy, Sivakumar; Alexander, Thomas; Balasubramanian, Padhmini

    2014-03-31

    Typhoid fever is caused by enteroinvasive Gram-negative organism Salmonella typhi. The well-known complications of typhoid fever are intestinal haemorrhage and perforation. In the pre-antibiotic era, these complications were quite common, but in the current antibiotic era the incidence of these complications is on the decline. We report a case of a patient with typhoid fever who developed haematochezia during the hospital stay and was found to have caecal ulcer with an adherent clot on colonoscopy. He was managed successfully with conservative measures without endotherapy and there was no rebleed.

  13. Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis.

    Science.gov (United States)

    Jaquenod De Giusti, Carolina; Ure, Agustín E; Rivadeneyra, Leonardo; Schattner, Mirta; Gomez, Ricardo M

    2015-08-01

    Macrophage influx and galectin 3 production have been suggested as major players driving acute inflammation and chronic fibrosis in many diseases. However, their involvement in the pathogenesis of viral myocarditis and subsequent cardiomyopathy are unknown. Our aim was to characterise the role of macrophages and galectin 3 on survival, clinical course, viral burden, acute pathology, and chronic fibrosis in coxsackievirus B3 (CVB3)-induced myocarditis. Our results showed that C3H/HeJ mice infected with CVB3 and depleted of macrophages by liposome-encapsulated clodronate treatment compared with infected untreated mice presented higher viral titres but reduced acute myocarditis and chronic fibrosis, compared with untreated infected mice. Increased galectin 3 transcriptional and translational expression levels correlated with CVB3 infection in macrophages and in non-depleted mice. Disruption of the galectin 3 gene did not affect viral titres but reduced acute myocarditis and chronic fibrosis compared with C57BL/6J wild-type mice. Similar results were observed after pharmacological inhibition of galectin 3 with N-acetyl-d-lactosamine in C3H/HeJ mice. Our results showed a critical role of macrophages and their galectin 3 in controlling acute viral-induced cardiac injury and the subsequent fibrosis. Moreover, the fact that pharmacological inhibition of galectin 3 induced similar results to macrophage depletion regarding the degree of acute cardiac inflammation and chronic fibrosis opens up the possibility of new pharmacological strategies for viral myocarditis.

  14. 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.

  15. 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.

  16. 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.

  17. Salmonella enterica serovar Typhi and the pathogenesis of typhoid fever.

    Science.gov (United States)

    Dougan, Gordon; Baker, Stephen

    2014-01-01

    Salmonella enterica serovar Typhi, the cause of typhoid, is host restricted to humans. S. Typhi has a monophyletic population structure, indicating that typhoid in humans is a relatively new disease. Antimicrobial usage is reshaping the current S. Typhi global population and may be driving the emergence of a specific haplotype, H58, that is well adapted to transmission in modern settings and is able to resist antimicrobial killing more efficiently than other S. Typhi. Evidence gathered through genomics and functional studies using the mouse and in vitro cell systems, together with clinical investigations, has provided insight into the mechanisms that underpin the pathogenesis of human typhoid and host restriction. Here we review the latest scientific advances in typhoid research and discuss how these novel approaches are changing our understanding of the disease.

  18. Scan Manifestations and Blood Clearance Rates in Typhoid Liver

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    Bahk, Yong Whee; Ahn, Jae Sung; Kim, Soon Hi [St. Mary' s Hospital, Catholic Medical College, Seoul (Korea, Republic of)

    1970-09-15

    Fourteen patients with typhoid fever studied by scanning and clearance-rate measurements of subcritical dose colloidal radiogold ({sup 198}Au). Mild to moderate enlargement of the liver and spleen was noted in 78.6 and 64.3 percent of patients, respectively; and splenic and spinal bone-marrow uptake was seen in 78.6 and 57.1 percent of cases, respectively. Typically, these scan changes occurred concomitantly (57.1%) and are considered to represent increased phagocytic activity of the RE cells which is characteristic of typhoid fever. The half clearance-time was significantly shortened during the first 10-day period of the illness indicating an increase in the hepatic blood in the early phase of typhoid infection. Hepatomegaly, splenomegaly and extrahepatic uptakes along with an accelerated (or less a normal) clearance time are characteristic of typhoid fever.

  19. A Case Report of Typhoidal Acute Acalculous Cholecystitis

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    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.

  20. Barriers to typhoid fever vaccine access in endemic countries

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    Khan MI

    2017-03-01

    Full Text Available M Imran Khan,1 Carlos Franco-Paredes,2,3 Sushant Sahastrabuddhe,4 R Leon Ochiai,5 Vittal Mogasale,4 Bradford D Gessner6 1Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan; 2Hospital Infantil de México, Federico Gómez, México DF., Mexico; 3Phoebe Putney Memorial Hospital, Albany, GA, USA; 4International Vaccine Institute, Seoul, Republic of Korea; 5Sanofi Pasteur, Lyon, 6Agence de Médecine Preventive, Ferney-Voltaire, France Abstract: Typhoid vaccines have been available as a means of disease control and prevention since 1896; however, their use as a routine tool for disease prevention in endemic settings has been hampered because of: 1 insufficient data on disease burden particularly regarding the lack of health care access in the poorest communities affected by typhoid; 2 limitations of the typhoid vaccine, such as shorter duration of protection, moderate efficacy in young children, and no efficacy for infants; 3 inadequate evidence on potential economic benefits when used for a larger population; 4 neglect in favor of alternative interventions that require massive infrastructure; 5 no financial support or commitment regarding vaccine delivery cost; 6 ambivalence about whether to invest in water and sanitation hygiene versus the vaccine; and 7 clarity on global policy for country adoption. If current typhoid-protein conjugate vaccines live up to their promise of higher efficacy, longer duration of protection, and efficacy in young children, typhoid vaccine use will be a critical component of short- and medium-term disease control strategies. Typhoid control could be accelerated if the global framework includes plans for accelerated introduction of the conjugate typhoid vaccine in developing countries. Keywords: typhoid fever, vaccines, policy, endemic countries, barriers, immunization

  1. Modeling malaria and typhoid fever co-infection dynamics.

    Science.gov (United States)

    Mutua, Jones M; Wang, Feng-Bin; Vaidya, Naveen K

    2015-06-01

    Malaria and typhoid are among the most endemic diseases, and thus, of major public health concerns in tropical developing countries. In addition to true co-infection of malaria and typhoid, false diagnoses due to similar signs and symptoms and false positive results in testing methods, leading to improper controls, are the major challenges on managing these diseases. In this study, we develop novel mathematical models describing the co-infection dynamics of malaria and typhoid. Through mathematical analyses of our models, we identify distinct features of typhoid and malaria infection dynamics as well as relationships associated to their co-infection. The global dynamics of typhoid can be determined by a single threshold (the typhoid basic reproduction number, R0(T)) while two thresholds (the malaria basic reproduction number, R0(M), and the extinction index, R0(MM)) are needed to determine the global dynamics of malaria. We demonstrate that by using efficient simultaneous prevention programs, the co-infection basic reproduction number, R0, can be brought down to below one, thereby eradicating the diseases. Using our model, we present illustrative numerical results with a case study in the Eastern Province of Kenya to quantify the possible false diagnosis resulting from this co-infection. In Kenya, despite having higher prevalence of typhoid, malaria is more problematic in terms of new infections and disease deaths. We find that false diagnosis-with higher possible cases for typhoid than malaria-cause significant devastating impacts on Kenyan societies. Our results demonstrate that both diseases need to be simultaneously managed for successful control of co-epidemics.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice.

    Science.gov (United States)

    Zhang, Min; Fei, Xia; Zhang, Guo-Qing; Zhang, Peng-Yu; Li, Feng; Bao, Wu-Ping; Zhang, Ying-Ying; Zhou, Xin

    2016-10-01

    Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.

  8. 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

  9. 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.

  10. A pilot study to examine the effect of chronic treatment with immunosuppressive drugs on mucociliary clearance in a vagotomized murine model.

    Directory of Open Access Journals (Sweden)

    Abhiram R Bhashyam

    Full Text Available BACKGROUND: Previously, we have demonstrated that mucociliary clearance (MCC is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation. METHODS: Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed were injected with three 100 µL injections of tacrolimus (1 mg/kg, mycophenolate mofetil (30 mg/kg, and prednisone (2 mg/kg once daily. Then, mice inhaled the radioisotope (99mtechnetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1-1.5 hrs and at 6-6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance. RESULTS: Although there was a slowing of MCC at 1-1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1-1.5 hrs for the two groups of mice. At 6-6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006. CONCLUSIONS: These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post

  11. 9 CFR 147.5 - The microagglutination test for pullorum-typhoid.

    Science.gov (United States)

    2010-01-01

    ... pullorum-typhoid. 147.5 Section 147.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... IMPROVEMENT PLAN Blood Testing Procedures § 147.5 The microagglutination test for pullorum-typhoid. Routinely...) or (e) of this section. (b) Stained microtest antigen for pullorum-typhoid is supplied...

  12. A novel technique for detecting antibiotic-resistant typhoid from rapid diagnostic tests.

    OpenAIRE

    2015-01-01

    Fluoroquinolone-resistant typhoid is increasing. An antigen-detecting rapid diagnostic test (RDT) can rapidly diagnose typhoid from blood cultures. A simple, inexpensive molecular technique performed with DNA from positive RDTs accurately identified gyrA mutations consistent with phenotypic susceptibility testing results. Field diagnosis combined with centralized molecular resistance testing could improve typhoid management and surveillance in low-resource settings.

  13. A Novel Technique for Detecting Antibiotic-Resistant Typhoid from Rapid Diagnostic Tests

    OpenAIRE

    2015-01-01

    Fluoroquinolone-resistant typhoid is increasing. An antigen-detecting rapid diagnotic test (RDT) can rapidly diagnose typhoid from blood cultures. A simple, inexpensive molecular technique performed with DNA from positive RDTs accurately identified gyrA mutations consistent with phenotypic susceptibility testing results. Field diagnosis combined with centralized molecular resistance testing could improve typhoid management and surveillance in low-resource settings.

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

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    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.

  15. Nested polymerase chain reaction for early diagnosis of typhoid fever.

    Science.gov (United States)

    Sultana, S; Hossain, M A; Alam, M A; Paul, S K; Mahmud, C; Kabir, M R; Haque, N; Yesmin, T; Kayes, M T; Maruf, A A; Kobayashi, N

    2012-01-01

    Typhoid fever, caused by Salmonella typhi, is an important cause of morbidity and mortality in many developing countries. A rapid and sensitive method for the detection of S. typhi is essential for early diagnosis. This was a study to prospectively evaluate the sensitivity and specificity of nested polymerase chain reaction (PCR) to identify the S. typhi using flagellin gene related primers. The study was carried out in the department of Microbiology, Mymensingh Medical College, Mymensingh between July, 2010 and June, 2011, including 82 individuals of different age and sex. Of them, 62 were clinically suspected cases of typhoid fever and remaining 20 were apparently healthy controls. Cultures as well as PCR of blood specimens were performed for each of the cases. Among the 62 suspected typhoid fever cases, 8(12.9%) were blood culture positive and 55(88.7%) were PCR positive for S. typhi. All culture positive cases were positive by PCR and among 54 culture negative cases, 47(87%) were positive by PCR. Neither of the healthy controls was positive by PCR or blood culture. The sensitivity, specificity, positive predictive value and negative predictive value of PCR using blood culture as gold standard were 88.7%, 100%, 100% and 74% respectively for typhoid fever. In this study, the PCR appears highly specific, very sensitive and superior to blood culture for the early diagnosis of typhoid fever.

  16. Increasing antimicrobial resistance and narrowing therapeutics in typhoidal salmonellae.

    Science.gov (United States)

    Kaurthe, Jaspal

    2013-03-01

    Multidrug-resistant typhoid fever (MDRTF) is a major public health problem in developing countries and is an emerging problem in the developed world. Because of the difficulties in preventing typhoid by public health measures or immunization in developing countries, great reliance is placed on antimicrobial chemotherapy. The treatment should commence as soon as the clinical diagnosis is made rather than after the results of antimicrobial susceptibility tests but the existence of MDRTF poses a serious clinical dilemma in the selection of empiric antimicrobial therapy. With the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin and trimethoprim, ciprofloxacin became the drug of choice for the treatment of typhoid fever. However, of late the efficacy of fluoroquinolones too has been questioned, mainly due to increasing reports of increasing defervescence time and poor patient response. This indicates that the organism has begun to develop resistance to fluoroquinolones, and is corroborated by a steady increase in Minimum Inhibitory Concentration (MIC) of ciprofloxacin. The therapeutics of ciprofloxacin-resistant enteric fever narrows down to third- and fourth-generation cephalosporins and azithromycin. However, the emergence of extended-spectrum b-lactamases (ESBLs) in typhoidal Salmonellae poses a new challenge and would greatly limit the therapeutic options leaving only tigecycline and carbepenems as secondary antimicrobial drugs. This increasing resistance is alarming and emphasizes the need of effective preventive measures to control typhoid and to limit the unnecessary use of antibiotics.

  17. Chronic murine myocarditis due to Trypanosoma cruzi: an ultrastructural study and immunochemical characterization of cardiac interstitial matrix

    Directory of Open Access Journals (Sweden)

    Sonia G. Andrade

    1986-03-01

    Full Text Available In an attempt to define the mouse-model for chronic Chagas' disease, a serological, histopathological and ultrastructural study as well as immunotyping of myocardium collagenic matrix were performed on Swiss mice, chronically infected with Trypanosoma cruzi strains: 21 SF and mambaí (Type II; PMN and Bolivia (Type III, spontaneously surviving after 154 to 468 days of infection. Haemagglutination and indirect immunofluorescence tests showed high titres of specific antibodies. The ultrastructural study disclosed the cellular constitution of the inflammatory infiltrate showing the predominance of monocytes, macrophages with intense phagocytic activity, fibroblasts, myofibroblasts and abundant collagen matrix suggesting the association of the inflammatory process with fibrogenesis in chronic chagasic cardiomyopathy. Artertolar and blood capillary alterations together with dissociation of cardiac cells from the capillary wall by edema and inflammation were related to ultrastructural lesions of myocardial cells. Rupture of parasitized cardiac myocells contribute to intensify the inflammatory process in focal areas. Collagen immunotyping showed the predominance of Types III and IV collagen. Collagen degradation and phagocytosis were present suggesting a reversibility of the fibrous process. The mouse model seems to be valuable in the study of the pathogenetic mechanisms in Chagas cardiomyopathy, providing that T. cruzi strains of low virulence and high pathogenecity are used.Utilizando o modelo experimental do camundongo, foi realizado um estudo sorológico, histopatológico e ultraestrutural bem como a imunotipagem do colágeno na matriz conjuntiva do miocárdio em camundongos suiços cronicamente infectados com as cepas 21 SF e Mambaí (Tipo II PMN e Bolívia (Tipo III por períodos de 154 a 468 dias. Os testes sorológicos e de imunofluorescência indireta mostraram altos títulos de anticorpos específicos. O estudo estrutural definiu melhor a

  18. Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease.

    Science.gov (United States)

    Lee, Jun Hee; Ryu, Jung Min; Han, Yong-Seok; Zia, Mohammad Farid; Kwon, Hyog Young; Noh, Hyunjin; Han, Ho Jae; Lee, Sang Hun

    2016-08-01

    Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-based therapy is a promising strategy for treatment of ischemic diseases associated with CKD, the associated pathophysiological conditions lead to low survival and proliferation of transplanted MSCs. To address these limitations, we investigated the effects of fucoidan, a sulfated polysaccharide, on the bioactivity of adipose tissue-derived MSCs and the potential of fucoidan-treated MSCs to improve neovascularization in ischemic tissues of CKD mice. Treatment of MSCs with fucoidan increased their proliferative potential and the expression of cell cycle-associated proteins, such as cyclin E, cyclin dependent kinase (CDK) 2, cyclin D1, and CDK4, via focal adhesion kinase and the phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt axis. Moreover, fucoidan enhanced the immunomodulatory activity of MSCs through the ERK-IDO-1 signal cascade. Fucoidan was found to augment the proliferation, incorporation, and endothelial differentiation of transplanted MSCs at ischemic sites in CKD mice hind limbs. In addition, transplantation of fucoidan-treated MSCs enhanced the ratio of blood flow and limb salvage in CKD mice with hind limb ischemia. To our knowledge, our findings are the first to reveal that fucoidan enhances the bioactivity of MSCs and improves their neovascularization in ischemic injured tissues of CKD. In conclusion, fucoidan-treated MSCs may provide an important pathway toward therapeutic neovascularization in patients with CKD.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

    Science.gov (United States)

    Non, Lemuel R; Patel, Rupa; Esmaeeli, Amir; Despotovic, Vladimir

    2015-11-01

    Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis.

  4. Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

    NARCIS (Netherlands)

    Vollaard, A.M.; Verspaget, H.W.; Ali, S.; Visser, L.G.; Veenendaal, R.A.; Asten, H.A.G.H. van; Widjaja, S.; Surjadi, C.; Dissel, J.T. van

    2006-01-01

    We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration

  5. Latex agglutination test (LAT) for the diagnosis of typhoid fever.

    Science.gov (United States)

    Sahni, Gopal Shankar

    2013-06-01

    The efficacy of latex agglutination test in the rapid diagnosis of typhoid fever was studied and the result compared with that of blood culture. This study included 80 children suffering from typhoid fever, among which 40 were confirmed by blood culture isolation and 40 had possible typhoid fever based on high Widal's titre (a four-fold rise in the titre of antibody to typhi "O" and "H" antigen was considered as a positive Widal's test result). Eighty children, 40 with febrile illness confirmed to be other than typhoid and 40 normal healthy children were used as negative controls. The various groups were: (i) Study group ie, group I had 40 children confirmed by culture isolation of Salmonella typhi(confirmed typhoid cases). (ii) Control groups ie, (a) group II with 40 febrile controls selected from paediatrics ward where cause other than S typhi has been established, (b) group III with 40 afebrile healthy controls that were siblings of the children admitted in paediatric ward for any reason with no history of fever and TAB vaccination in the last one year, and (c) group IV with 40 children with high Widal's titre in paired sera sample. Widal's test with paired sera with a one week interval between collections were done in all 40 patients. Latex aggtutination test which could detect 900 ng/ml of antigen as observed in checker board titration, was positive in all 40 children from group I who had positive blood culture and in 30 children from group IV who had culture negative and had high Widal's titre positive. Latex agglutination test was positive in 4 children in group II and none in group III. Using blood culture positive cases as true positive and children in groups II and III as true negative, the test had a sensitivity of 100% and specificity of 96%. Latex agglutination test was found to be significantly sensitive (100%) and specific (96%) and could detect 75% more cases in group IV (possible typhoid cases). Thus latex agglutination test can be used for rapid

  6. 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.

  7. Murine Typhus

    Science.gov (United States)

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. 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. PMID:24893060

  8. 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.

  9. 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.

  10. The emergence and outbreak of multidrug-resistant typhoid fever in China.

    Science.gov (United States)

    Yan, Meiying; Li, Xinlan; Liao, Qiaohong; Li, Fang; Zhang, Jing; Kan, Biao

    2016-06-22

    Typhoid fever remains a severe public health problem in developing countries. The emergence of resistant typhoid, particularly multidrug-resistant typhoid infections, highlights the necessity of monitoring the resistance characteristics of this invasive pathogen. In this study, we report a typhoid fever outbreak caused by multidrug-resistant Salmonella enterica serovar Typhi strains with an ACSSxtT pattern. Resistance genes conferring these phenotypes were harbored by a large conjugative plasmid, which increases the threat of Salmonella Typhi and thus requires close surveillance for dissemination of strains containing such genes.

  11. [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.

  12. 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.

  13. [Pleuropulmonary localizations of non-typhoid Salmonella infections].

    Science.gov (United States)

    Le Chevalier, B; Jehan, A; Brun, J; Vergnaud, M

    1985-01-01

    Non-typhoid salmonella infections are extremely common, usually taking the form of a benign toxi-infection. In the context of the rare extra-digestive manifestations, the authors report 3 cases of pleuro-pulmonary involvement, in infections due to Salmonella Dublin. In 2 cases, the organism was identified from blood cultures, whilst in the 3rd case it was isolated from pleural fluid. As with other extra-digestive sites, pleuro-pulmonary involvement is favored by underlying pathology, accounting for the grave nature of the problem (amongst the 3 cases, gastrectomy and acute myeloblastic leukemia in one case and obliterative arterial disease in another case). Non-typhoid salmonella infections are sensitive to Sulfamethoxazole-trimethoprim which diffuses well in the respiratory system. They are also sensitive to Amoxicillin and to Chloramphenicol.

  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. 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.

  16. 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

  17. 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.

  18. Typhoid Fever in nineteenth-century Colombia: between medical geography and bacteriology.

    Science.gov (United States)

    García, Mónica

    2014-01-01

    This paper analyses how the Colombian medical elites made sense of typhoid fever before and during the inception of bacteriological ideas and practices in the second half of the nineteenth century. Assuming that the identity of typhoid fever has to be understood within the broader concerns of the medical community in question, I show how doctors first identified Bogotá's epidemics as typhoid fever during the 1850s, and how they also attached specificity to the fever amongst other continuous fevers, such as its European and North American counterparts. I also found that, in contrast with the discussions amongst their colleagues from other countries, debates about typhoid fever in 1860-70 among doctors in Colombia were framed within the medico-geographical scheme and strongly shaped by the fear of typhoid fever appearing alongside 'paludic' fevers in the highlands. By arguing in medico-geographical and clinical terms that typhoid fever had specificity in Colombia, and by denying the medico-geographical law of antagonism between typhoid and paludic fevers proposed by the Frenchman Charles Boudin, Colombian doctors managed to question European knowledge and claimed that typhoid fever had distinct features in Colombia. The focus on paludic and typhoid fevers in the highlands might explain why the bacteriological aetiology of typhoid fever was ignored and even contested during the 1880s. Anti-Pasteurian arguments were raised against its germ identity and some physicians even supported the idea of spontaneous origin of the disease. By the 1890s, Pasteurian knowledge had come to shape clinical and hygienic practices.

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

    Science.gov (United States)

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

    2015-06-01

    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.

  20. Typhoid carrier state and risk of gallbladder cancer%伤寒带菌与胆囊癌形成

    Institute of Scientific and Technical Information of China (English)

    高诗会; 赵英伟

    2012-01-01

    Typhoid is a global concern. About 21 million people are infected by Salmonella typhi (S. typhi) every year, and nearly 5% of them become chronic carriers. Current studies indicate that chronic S. typhi infection is associated with gallstone and gallbladder cancer, a relatively rare neoplasm with increasing incidence rates in certain populations. The incidence rates of gallstone and gallbladder cancer are two-fold higher in women than in men. The chronic carrier state is a risk factor not only for gallbladder cancer but also for other cancers in some extent. The research on relationships among typhoid carrier state, biofilm and gallstone formation, and gallbladder cancer are reviewed in this paper.%近年来,世界范围内伤寒发病人数有所上升,每年大约有2100万人感染,近5%感染者会发展成慢性带菌者.慢性带菌状态发展成胆结石的危险性很高,胆结石表面形成的生物膜有助于保持慢性带菌状态,进而可能发展成胆囊癌.胆囊癌比较少见,但在某些国家和地区发病率高,且女性胆结石和胆囊癌的发病率是男性的2倍多.慢性带菌状态不仅是胆囊癌发生的危险因素,也是其他癌症发生的危险因素.本文就伤寒带菌状态与生物膜和胆结石的形成及发展成胆囊癌的相关性研究进行综述.

  1. 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.)

  2. A plausible explanation for male dominance in typhoid ileal perforation

    Directory of Open Access Journals (Sweden)

    Khan M

    2012-11-01

    Full Text Available Mohammad KhanDepartment of Microbiology, College of Medicine, Chichiri, Blantyre, MalawiAbstract: The phenomenon of consistent male dominance in typhoid ileal perforation (TIP is not well understood. It cannot be explained on the basis of microbial virulence, Peyer's patch anatomy, ileal wall thickness, gastric acidity, host genetic factors, or sex-linked bias in hospital attendance. The cytokine response to an intestinal infection in males is predominantly proinflammatory as compared with that in females, presumably due to differences in the sex hormonal milieu. Sex hormone receptors have been detected on lymphocytes and macrophages, including on Peyer's patches, inflammation of which (probably similar to the Shwartzman reaction/Koch phenomenon is the forerunner of TIP, and is not excluded from the regulatory effects of sex hormones. Hormonal control of host-pathogen interaction may override genetic control. Environmental exposure to Salmonella typhi may be more frequent in males, presumably due to sex-linked differences in hygiene practices and dining-out behavior. A plausible explanation of male dominance in TIP could include sex-linked differences in the degree of natural exposure of Peyer's patches to S. typhi. An alternative explanation may include sexual dimorphism in host inflammatory response patterns in Peyer's patches that have been induced by S. typhi. Both hypotheses are testable.Keywords: explanation, dominance, male, perforation, ileum, typhoid

  3. 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...... 2·4–4·2) forin-patients with gastroenteritis, and 1·6 (95% CI 1·0–2·8) for in-patients with bacteraemia. We conclude that the role of seasonal variation diminishes with increased severity of non-typhoidSalmonella infection....

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

    Directory of Open Access Journals (Sweden)

    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

  5. Near-fatal myocarditis complicating typhoid fever in a traveler returning from Nepal.

    Science.gov (United States)

    Palombo, Michal; Margalit-Yehuda, Reuma; Leshem, Eyal; Sidi, Yechezkel; Schwartz, Eli

    2013-01-01

    We report a 27-year-old traveler who returned from Nepal suffering from typhoid fever. His disease was complicated by life-threatening myocarditis and ventricular fibrillation, a rare manifestation in travelers.

  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. Cholestatic hepatitis in a patient with typhoid fever - a case report

    Directory of Open Access Journals (Sweden)

    Wijesiriwardena Bandula C

    2011-10-01

    Full Text Available Abstract Typhoid fever is a very common infectious disease, particularly in developing countries such as Sri Lanka. Although multiple organs are known to be affected by the disease, hepatic involvement could be considered the most important as studies have showed that it is associated with a higher relapse rate. We report a young patient who presented with fever and jaundice and found to have cholestatic hepatitis secondary to typhoid fever.

  8. Study of Serum Alanine Transaminase: Serum Lactate Dehydrogenase Ratio for Typhoid Hepatits

    OpenAIRE

    Damor PB; Prajapati VJ; Patel SV; Vasavada H; Panchal AR; Shukla P

    2016-01-01

    "Introduction: Typhoid hepatitis clinically mimics acute viral hepatitis. Differentiation between these two illnesses is very important as typhoid hepatitis requires definitive treatment in form of antimicrobial drugs. This study was undertaken to study pattern of hepatic involvement in enteric fever and to evaluate serum ALT:LDH ratio for differentiating it from acute viral hepatitis. Material and Method :This was a clinical observational study .Patients of enteric fever with hepatic mani...

  9. 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.

  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. Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

    Science.gov (United States)

    Wardhana; Surachmanto, Eko E; Datau, E A

    2013-10-01

    Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

  12. Immunoproteomic analysis of antibody in lymphocyte supernatant in patients with typhoid fever in Bangladesh.

    Science.gov (United States)

    Charles, Richelle C; Liang, Li; Khanam, Farhana; Sayeed, M Abu; Hung, Chris; Leung, Daniel T; Baker, Stephen; Ludwig, Albrecht; Harris, Jason B; Larocque, Regina C; Calderwood, Stephen B; Qadri, Firdausi; Felgner, Philip L; Ryan, Edward T

    2014-03-01

    We have previously shown that an assay based on detection of anti-Salmonella enterica serotype Typhi antibodies in supernatant of lymphocytes harvested from patients presenting with typhoid fever (antibody in lymphocyte supernatant [ALS] assay) can identify 100% of patients with blood culture-confirmed typhoid fever in Bangladesh. In order to define immunodominant proteins within the S. Typhi membrane preparation used as antigen in these prior studies and to identify potential biomarkers unique to S. Typhi bacteremic patients, we probed microarrays containing 2,724 S. Typhi proteins with ALS collected at the time of clinical presentation from 10 Bangladeshis with acute typhoid fever. We identified 62 immunoreactive antigens when evaluating both the IgG and IgA responses. Immune responses to 10 of these antigens discriminated between individuals with acute typhoid infection and healthy control individuals from areas where typhoid infection is endemic, as well as Bangladeshi patients presenting with fever who were subsequently confirmed to have a nontyphoid illness. Using an ALS enzyme-linked immunosorbent assay (ELISA) format and purified antigen, we then confirmed that immune responses against the antigen with the highest immunoreactivity (hemolysin E [HlyE]) correctly identified individuals with acute typhoid or paratyphoid fever in Dhaka, Bangladesh. These observations suggest that purified antigens could be used with ALS and corresponding acute-phase activated B lymphocytes in diagnostic platforms to identify acutely infected patients, even in areas where enteric fever is endemic.

  13. 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.

  14. Epidemiological analysis of typhoid fever in Kelantan from a retrieved registry

    Directory of Open Access Journals (Sweden)

    Ismail, A.

    2013-01-01

    Full Text Available Aim: Despite the endemicity of typhoid in Kelantan, epidemiological data showing typhoid association to age, sex,ethnicity and district of patients is limited. This retrospective study investigated the statistical association of thesevariables from a retrieved registry.Methodology and results: Cross-tabulation using SPSS was used to analyze 1394 cases of confirmed typhoid patientsadmitted to various hospitals in Kelantan state over a six-year period. Fourteen age groups with a five-year rangeinterval were generated. There was a significant association between typhoid infection and sex of subjects, wherebyfemales were generally more susceptible than males. Ethnicity and district of typhoid patients did not show significantassociation.Conclusion, significance and impact of study: The observation of an increased number of typhoid cases with a malepredominance in the age group 5-14 and female predominance in the 20-60 age group calls for improved hygiene,continued public health education, together with better laboratory diagnostics to identify carriers, are some measures tocontrol this disease.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

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

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    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.

  18. 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...

  19. 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

  20. Role of Abdominal Ultrasound in the Diagnosis of Typhoid Fever in Pediatric Patients

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    Niranjan Sahu

    2016-12-01

    Full Text Available An early diagnosis of typhoid fever caused by Salmonella typhi is difficult because of several spectra of clinical findings, identical to those of several other types of infections. A definitive diagnosis of typhoid fever is made by hemoculture as well as the Widal test. With pediatric patients, this life-threatening infection remains inherently long enough, demanding urgent attention. In typhoid fever, splenomegaly, enlarged mesenteric lymph nodes (MLNs, bowel wall thickening, acalculus cholecystitis, and hepatomegaly occur, which are diagnosed by the ultrasonography (USG test. USG is a noninvasive, easily available, economical, fairly acceptable, and fairly sensitive test. The high-resolution real-time gray-scale USG method has simplified the evaluation of pathologic conditions, with remarkable clarity; consequently, an accurate assessment of the associated lesions can be done. In typhoid-endemic areas, USG findings as cited above could be used for diagnosis of typhoid fever, particularly when serology is equivocal and hemocultures are negative or not available. It was evident from USG studies that 12 of 52 patients had calculus cholecystitis; these individuals as well as eight patients without cholecystitis having hemocultures negative for S. typhi were excluded from the study. The rest of the cases (n=32 were included in this USG-based study for evaluation of features specific for typhoid fever. The following observations were recorded: splenomegaly in 32 patients, enlarged MLNs in 30 patients, bowel wall thickening in 25 patients, acalculus cholecystitis in 20 patients, and hepatomegaly in 10 patients. It can be concluded that these USG features—hepatosplenomegaly, enlarged MLNs, bowel wall thickening, and acalculus cholecystitis—should strongly favor the diagnosis of typhoid.

  1. 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.

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

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    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

  3. 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

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

    NARCIS (Netherlands)

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

    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

  5. 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.

  6. 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.

  7. 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.

  8. A COMPARATIVE STUDY OF TYPHIDOT AND WIDAL TEST IN T HE DIAGNOSIS OF TYPHOID FEVER

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    Balakrishna

    2013-05-01

    Full Text Available ABSTRACT:- AIM AND OBJECTIVES: Purpose of the study is to compare the sensitivity and specificity of Widal test and Typhi dot with the bl ood culture, in the diagnosis of Typhoid fever. Material and methods:- Blood samples from 200 clini cally diagnosed typhoid cases, were subjected to blood culture and the isolates were identified b y biochemical reactions and samples were subjected to serological tests, Widal test and Typh i dot test. RESULTS: Out of 200 clinically diagnosed typhoid cases, 28 (14% were blood cultur e positive for Salmonella typhi, 43 (21.5% were Widal positive and 55 (27.5% were Typhi dot p ositive. CONCLUSION : Blood culture and Widal test are used as conventional methods in the diagnosis of the typhoid fever. Typhi dot test is a new rapid serological test introduced commerciall y for the diagnosis typhoid fever. Typhi dot test has been designed to detect the IgM and IgG antibod ies against the outer membrane protein (OMP of Salmonella typhi. It offers the advantage of rapid & early diagnosis , with a sensitivity & specificity of 92% & 83% respectively in culture proven cases.

  9. 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

    2011-11-08

    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.

  10. Current antimicrobial sensitivity pattern of typhoidal salmonellae in a referral diagnostic centre

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    Umer Shujat

    2016-03-01

    Full Text Available Background: Infections caused by typhoidal salmonellae are an important public health concern in Pakistan. Inappropriate and injudicious use of fluoroquinolones has reduced their efficacy due to development of high level resistance. Aim: To ascertain the current susceptibility pattern of typhoidal salmonellae thus guiding the physicians for better management of typhoid patients.Materials and Methods: A study was conducted at our institution from January 2012 through December 2013 to investigate current susceptibility pattern of typhoidal salmonellae. Results: Out of 200 isolates, 107 (53.5% were identified as Salmonella Typhi and 93 (46.5% as Salmonella Paratyphi A. Sensitivities of Salmonella Typhi were as follows: ampicillin (48.6%, chloramphenicol (45.8%, co-trimoxazole (40.1%, ciprofloxacin (11.2%. Sensitivities of Salmonella Paratyphi A were: ampicillin (80.6%, chloramphenicol (89.2%, co-trimoxazole (90.3%, and ciprofloxacin (16.1%. No resistance was detected against third generation cephalosporins. Conclusions: Typhoidal salmonellae are still entirely susceptible to third generation cephalosporins in our setting. Marked rise in resistance to fluoroquinolones has reduced their empirical usage. Sensitivity of Salmonella Paratyphi A to conventional antityphoid drugs was encouraging.

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

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    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.

  12. 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.

  13. Heavy Chain-Hyaluronan/Pentraxin 3 from Amniotic Membrane Suppresses Inflammation and Scarring in Murine Lacrimal Gland and Conjunctiva of Chronic Graft-versus-Host Disease

    Science.gov (United States)

    Ogawa, Yoko; He, Hua; Mukai, Shin; Imada, Toshihiro; Nakamura, Shigeru; Su, Chen-Wei; Mahabole, Megha; Tseng, Scheffer C. G.; Tsubota, Kazuo

    2017-01-01

    Chronic graft-versus-host disease (cGVHD) is a major complication of hematopoietic stem cell transplantation. Dry eye disease is the prominent ocular sequel of cGVHD and is caused by excessive inflammation and fibrosis in the lacrimal glands. Heavy chain-Hyaluronan/Pentraxin 3 (HC-HA/PTX3) is a complex purified from human amniotic membrane (AM) and known to exert anti-inflammatory and anti-scarring actions. In this study, we utilized a mouse model of cGVHD to examine whether HC-HA/PTX3 could attenuate dry eye disease elicited by cGVHD. Our results indicated that subconjunctival and subcutaneous injection of HC-HA/PTX3 preserved tear secretion and conjunctival goblet cell density and mitigated inflammation and scarring of the conjunctiva. Such therapeutic benefits were associated with suppression of scarring and infiltration of inflammatory/immune cells in the lacrimal glands. Furthermore, HC-HA/PTX3 significantly reduced the extent of infiltration of CD45+ CD4+ IL-17+ cells, CD45+ CD34+ collagen I+ CXCR4+ fibrocytes, and HSP47+ activated fibroblasts that were accompanied by upregulation of collagen type Iα1, collagen type IIIα1 and NF-kB in lacrimal glands. Collectively, these pre-clinical data help prove the concept that subcutaneous and subconjunctival injection of HC-HA/PTX3 is a novel approach to prevent dry eye disease caused by cGVHD and allow us to test its safety and efficacy in future human clinical trials. PMID:28165063

  14. 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

  15. Food panics in history: corned beef, typhoid and "risk society".

    Science.gov (United States)

    Smith, David F

    2007-07-01

    An outline of the "risk society" thesis of the German social theorist Ulrich Beck is given, and some points that he has taken from food safety examples are discussed. The potential for exploring the viability and utility of the thesis, via a comparative study of historical food safety episodes is illustrated through an account and discussion of the large corned beef-associated typhoid outbreak which occurred in 1964 in Aberdeen, Scotland. The outcome of the Aberdeen affair, in terms of public and political interest in food safety, and impact on the official food safety system, is compared with the outcome and impact of the series of food safety episodes of the 1980s and 1990s. The interactions between the latter episodes and the new food movement, the proactive responses of corporate interests, and the dramatic changes in the food safety regime represented by the formation of the Food Standards Agency in Britain, are contrasted with the relative lack of impact of the Aberdeen outbreak. Despite criticisms of Beck's thesis, this comparative study highlights, in particular, the value of his concept of "subpolitics", and his expectation that the transition to risk society will involve the emergence of new social institutions. Such insights may help orientate epidemiologists and community health specialists who are currently active in food safety and regulation.

  16. A plausible explanation for male dominance in typhoid ileal perforation.

    Science.gov (United States)

    Khan, Mohammad

    2012-01-01

    The phenomenon of consistent male dominance in typhoid ileal perforation (TIP) is not well understood. It cannot be explained on the basis of microbial virulence, Peyer's patch anatomy, ileal wall thickness, gastric acidity, host genetic factors, or sex-linked bias in hospital attendance. The cytokine response to an intestinal infection in males is predominantly proinflammatory as compared with that in females, presumably due to differences in the sex hormonal milieu. Sex hormone receptors have been detected on lymphocytes and macrophages, including on Peyer's patches, inflammation of which (probably similar to the Shwartzman reaction/Koch phenomenon) is the forerunner of TIP, and is not excluded from the regulatory effects of sex hormones. Hormonal control of host-pathogen interaction may override genetic control. Environmental exposure to Salmonella typhi may be more frequent in males, presumably due to sex-linked differences in hygiene practices and dining-out behavior. A plausible explanation of male dominance in TIP could include sex-linked differences in the degree of natural exposure of Peyer's patches to S. typhi. An alternative explanation may include sexual dimorphism in host inflammatory response patterns in Peyer's patches that have been induced by S. typhi. Both hypotheses are testable.

  17. 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.

  18. 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.

  19. A Salmonella Typhi homologue of bacteriophage muramidases controls typhoid toxin secretion.

    Science.gov (United States)

    Hodak, Hélène; Galán, Jorge E

    2013-01-01

    Unlike other Salmonella, which can infect a broad range of hosts causing self-limiting infection, Salmonella Typhi is an exclusively human pathogen that causes typhoid fever, a life-threatening systemic disease. Typhoid toxin is a unique virulence factor of Salmonella Typhi, which is expressed when the bacteria are within mammalian cells. Here, we report that an N-acetyl-β-D-muramidase similar to phage endolysins encoded within the same pathogenicity islet as the toxin is required for typhoid toxin secretion. Genetic and functional analysis of TtsA revealed unique amino acids at its predicted peptidoglycan-binding domain that are essential for protein secretion and that distinguishes this protein from other homologues. We propose that TtsA defines a new protein secretion mechanism recently evolved from the machine that mediates phage release.

  20. Peritonitis secondary to ruptured splenic abscess: a grave complication of typhoid fever.

    Science.gov (United States)

    George, Peter; Ahmed, Ashfaq; Maroli, Roshan; Tauro, Leo Francis

    2012-12-01

    Splenic abscesses are increasingly being identified, possibly due to widespread use of imaging modalities in clinical practice. The commonest clinical features are high grade fever and exclusively localised left upper quadrant abdominal pain. These symptoms are similar to most infectious diseases prevalent in the tropics, making imaging by ultrasonography or computer tomography a necessity in the diagnosis. There are reports from different geographic areas on splenic abscesses associated with typhoid fever. We reported ruptured splenic abscess presenting with peritonitis as a rare and grave complication of typhoid fever.

  1. Peritonitis secondary to ruptured splenic abscess:A grave complication of typhoid fever

    Institute of Scientific and Technical Information of China (English)

    Peter George; Ashfaq Ahmed; Roshan Maroli; Leo Francis Tauro

    2012-01-01

    Splenic abscesses are increasingly being identified, possibly due to widespread use of imaging modalities in clinical practice. The commonest clinical features are high grade fever and exclusively localised left upper quadrant abdominal pain. These symptoms are similar to most infectious diseases prevalent in the tropics, making imaging by ultrasonography or computer tomography a necessity in the diagnosis. There are reports from different geographic areas on splenic abscesses associated with typhoid fever. We reported ruptured splenic abscess presenting with peritonitis as a rare and grave complication of typhoid fever.

  2. 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.

  3. Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis

    OpenAIRE

    2003-01-01

    The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated...

  4. Proteomics Analysis of the Causative Agent of Typhoid Fever

    Energy Technology Data Exchange (ETDEWEB)

    Ansong, Charles; Yoon, Hyunjin; Norbeck, Angela D.; Gustin, Jean K.; McDermott, Jason E.; Mottaz, Heather M.; Rue, Joanne; Adkins, Joshua N.; Heffron, Fred; Smith, Richard D.

    2008-02-01

    Typhoid fever is a potentially fatal disease caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. typhi). S. typhi infection is a complex process that involves numerous bacterially-encoded virulence determinants, and these are thought to confer both stringent human host specificity and a high mortality rate. In the present study we used a liquid chromatography-mass spectrometry (LC-MS) based proteomics strategy to investigate the proteome of logarithmic, stationary phase, and low pH/low magnesium (MgM) S. typhi cultures. This represents the first large scale comprehensive characterization of the S. typhi proteome. Our analysis identified a total of 2066 S. typhi proteins. In an effort to identify putative S. typhi-specific virulence factors, we then compared our S. typhi results to those obtained in a previously published study of the S. typhimurium proteome under similar conditions (Adkins J.N. et al (2006) Mol Cell Prot). Comparative proteomic analysis of S. typhi (strain Ty2) and S. typhimurium (strains LT2 and 14028) revealed a subset of highly expressed proteins unique to S. typhi that were exclusively detected under conditions that mimic the infective state in macrophage cells. These proteins included CdtB, HlyE, and a conserved protein encoded by t1476. The differential expression of selected proteins was confirmed by Western blot analysis. Taken together with the current literature, our observations suggest that this subset of proteins may play a role in S. typhi pathogenesis and human host specificity. In addition, we observed products of the biotin (bio) operon displayed a higher abundance in the more virulent strains S. typhi-Ty2 and S. typhimurium-14028 compared to the virulence attenuated S. typhimurium strain LT2, suggesting bio proteins may contribute to Salmonella pathogenesis.

  5. 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.

  6. The burden of typhoid fever in low- and middle-income countries: A meta-regression approach

    Science.gov (United States)

    Warren, Joshua L.; Crawford, Forrest W.; Weinberger, Daniel M.; Kürüm, Esra; Pak, Gi Deok; Marks, Florian; Pitzer, Virginia E.

    2017-01-01

    Background Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. Methods We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. Results We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9–48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2–4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. Conclusions Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases. PMID:28241011

  7. 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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    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.

  11. 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.

  12. 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.

  13. 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...

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

    NARCIS (Netherlands)

    Santen, S. van; Mast, Q. de; Swinkels, D.W.; Ven, A.J.A.M. van der

    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 cofactor in this association. Malarial disease, among others, is associated with enhanced erythrophagocytos

  15. Colonoscopic findings and management of patients with outbreak typhoid fever presenting with lower gastrointestinal bleeding.

    Science.gov (United States)

    Shaikhani, Mohammad A R; Husein, Hiwa A B; Karbuli, Taha A; Mohamed, Mohamed Abdulrahman

    2013-09-01

    Lower gastrointestinal bleeding (LGIB) along with intestinal perforation is a well-known complication of typhoid fever. Reports of colonoscopic appearance and intervention of typhoid perforation involve only few cases. This series reports the colonoscopic findings and the role of colonoscopic hemostatic interventions in controlling the bleeding ileocolonic lesions. During the typhoid fever outbreak in Sulaymaniyah City in Iraqi Kurdistan Region, we received 52 patients with LGIB manifesting as fresh bleeding per rectum or melena. We performed total colonoscopy with ileal intubation for all cases. The findings were recorded and endoscopic hemostatic intervention with adrenaline-saline injection and argon plasma coagulation was applied to actively bleeding lesion. These patients were young, 11-30 years of age, with female preponderance. Blood culture was positive in 50 %. Colonoscopic findings were mostly located in the ileocecal region, although other areas of the colon were involved in many cases. Twenty-four percent of the cases required endoscopic hemostatic intervention by adrenaline injection with argon plasma coagulation which was effective in all patients except one who died in spite of surgical intervention in addition of endoscopic hemostasis. Dual endoscopic hemostatic intervention can be a safe and effective management option for patients with LGIB due to typhoid fever.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  17. [The surgical complications of typhoid fever: a report of 10 cases].

    Science.gov (United States)

    González Ojeda, A; Pérez Ríos, A; Rodríguez, M; de la Garza Villaseñor, L

    1991-01-01

    This is a retrospective review of 10 consecutive patients with intra-abdominal complications of typhoid fever requiring surgical treatment, during a four-year period at the Instituto Nacional de la Nutrición Salvador Zubirán. There were 7 males and 3 females with an average age of 33.9 years. In 80 per cent of the cases Salmonella typhi was obtained in blood and bone narrow cultures. Five cases developed terminal ileum perforations, 4 massive bleeding related to ulcerated typhoid ileitis and one patient was operated on with the preoperative diagnosis of acute abdomen during the course of severe, toxic, typhoid fever. At laparotomy, no abnormalities were found. Five patients were treated with right hemicolectomy, 3 with local resections and primary closure, and another one, with segmental terminal ileum resection and end to end anastomosis. One patient died of mixed shock and multiple organ failure. This event was secondary to partial dehiscence of the ileo-transverse anastomosis and massive bleeding. Four patients had complications; a) pneumonia, b) urinary tract infection, c) splenic abscess that required splenectomy and: d) intestinal obstruction. All patients were treated with chloramphenicol. We found a high morbidity and mortality rate of the typhoid fever complications. The surgical resection and specific antibiotic therapy are the most effective treatment, however, complications can appear during its treatment.

  18. Non-typhoidal Salmonella group D bacteremia and urosepsis in a patient diagnosed with HIV Infection

    Directory of Open Access Journals (Sweden)

    Said Abuhasna

    2012-01-01

    Full Text Available Urinary tract infections caused by non-typhoid Salmonella are rare and usually develops in patients with predisposing factors such as immune deficiency or occult urologic problems. This report describes a case where Salmonella Group D was isolated from the blood and urine of a patient with documented human acquired immunodeficiency syndrome who developed urosepsis and was successfully treated with antibiotics.

  19. Non-typhoidal Salmonella group D bacteremia and urosepsis in a patient diagnosed with HIV Infection.

    Science.gov (United States)

    Abuhasna, Said; Al Jundi, Amer; Rahman, Masood Ur; Said, Walaa

    2012-10-01

    Urinary tract infections caused by non-typhoid Salmonella are rare and usually develops in patients with predisposing factors such as immune deficiency or occult urologic problems. This report describes a case where Salmonella Group D was isolated from the blood and urine of a patient with documented human acquired immunodeficiency syndrome who developed urosepsis and was successfully treated with antibiotics.

  20. 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.

  1. 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

  2. Lifestyles and practices that enhance malaria and typhoid fever in Njoro District, Kenya.

    Science.gov (United States)

    Kinuthia, Geoffrey Kariuki; Gicheru, Michael Muita; Ngure, Peter Kamau; Kabiru, Ephantus Wanjohi

    2012-02-01

    Unhygienic practices have been associated with the spread of parasitic and bacterial infections in rural areas. This study was designed to verify the link between the frequencies of malaria and typhoid fever with selected rural practices in Njoro District, Kenya. A cross-sectional study involving observations, questionnaires and interviews was conducted to determine the socio-economic variables and practices/lifestyles in 336 randomly selected homesteads. Frequencies of malaria and typhoid fever in two randomly selected health centers were determined through a retrospective study for the period from 2004 to 2009. The respondents had large families (68%), low education level (67%) and high responsibility burden (67%). Individuals who did not boil drinking water constituted 61%. Boiling drinking water was less common among the poor, Odds Ratio (OR) of 2.36, χ(2) = 9.88, 95% Confidence Interval (CI) of 1.38-4.03. Respondents who washed their hands in a basin after using the latrines comprised 79.8% while 4.8% did not. 18.5% of the respondents did not use a soap to wash their hands after using the latrine. One third (33.6%) of the homesteads had dirty and inappropriate pit latrines while 2.7% of the homesteads lacked latrines. Failure to use mosquito bed nets was more likely to occur among the poor respondents, OR of 1.44, χ(2) = 1.74, 95% CI of 0.84-2.48. The frequencies of malaria and typhoid fever were an average of 29 and 24% respectively. Malaria and typhoid fever cases were relatively frequent due to adoption of inappropriate lifestyles and practices that predisposed the residents to infectious agents. Poverty seemed to play a significant role in the spread of malaria and typhoid fever.

  3. Clinical Efficacy of Azithromycin in Typhoid and Paratyphoid Fever in Children

    Directory of Open Access Journals (Sweden)

    Md Atiqul Islam

    2015-01-01

    Full Text Available Background: Azithromycin sensitivity cannot precisely identify the strains of typhoid and paratyphoid fever for successful treatment. Most of the studies show that azithromycin is highly effective in uncomplicated typhoid fever. Very few studies have been carried out in Bangladesh to see the effectiveness and sensitivity of azithromycin in children with uncomplicated typhoid fever. Objective: To assess the clinical response of azithromycin in uncomplicated typhoid fever. Materials and Methods: This randomized clinical trial was conducted in Dhaka Shishu (children Hospital from January to December 2009. Children between 2–12 years of age with characteristic clinical presentation of uncomplicated typhoid fever with positive blood culture for S. typhi or S. paratyphi were included in this study. Patients were treated with oral azithromycin 20 mg/kg/day for 7 days in one group and intravenous ceftriaxone 100 mg/kg/day in another group. Effectiveness and sensitivity pattern were documented and compared. Results: Fifty patients were allocated randomly with azithromycin and 48 with ceftriaxone. Twenty two percent of the subjects were below 5 years and 78% above 5 years. Average time of defervescence was 4.44 ± 1.25 days in azithromycin group and 4.38 ± 1.21 days in ceftriaxone group. Response to treatment in both groups was excellent: 94% in azithromycin and 97.9% in ceftriaxone groups. The occurrence of complication was very low in both groups. Eighteen percent showed resistance to azithromycin and 2.1% to ceftriaxone. In azithromycin sensitive group 97.6% showed improvement and in resistant group 77.8% showed improvement. A good percentage of patients who were resistant to azithromycin showed clinical improvement following treatment with this drug. Conclusion: Current study recommends that azithromycin is effective in the treatment of enteric fever in children. The study also shows that some patients resistant to azithromycin showed clinical

  4. 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

    2014-10-03

    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.

  5. 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...

  6. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.

    Science.gov (United States)

    Mooney, Jason P; Lokken, Kristen L; Byndloss, Mariana X; George, Michael D; Velazquez, Eric M; Faber, Franziska; Butler, Brian P; Walker, Gregory T; Ali, Mohamed M; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M M; Luckhart, Shirley; Tsolis, Renée M

    2015-10-05

    Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.

  7. 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

  8. Poultry as a possible source of non-typhoidal Salmonella enterica serovars in humans in Bangladesh.

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    Barua, Himel; Biswas, Paritosh Kumar; Talukder, Kaisar Ali; Olsen, Katharina E P; Christensen, Jens Peter

    2014-01-31

    We investigated Salmonella enterica isolates from human clinical cases of gastroenteritis to determine the distribution of non-typhoidal Salmonella serovars in the human population, and compared them to isolates originating from poultry by serotyping, phage typing, plasmid profiling, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) to evaluate the potential role of poultry in human non-typhoidal salmonellosis in Bangladesh. Nine different serovars were identified among the human isolates of which Salmonella Paratyphi B var Java (S. Java), S. Kentucky, S. Enteritidis, S. Virchow and S. Weltevreden also were commonly isolated from poultry. The poultry isolates belonging to S. Java, S. Kentucky and S. Enteritidis were indistinguishable from human isolates or genetically closely related, based on PFGE profiles and MLST. S. Kentucky clone ST198 and S. Java clone ST43 both well-known cause of human infections were also isolated from poultry.

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

    OpenAIRE

    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...

  10. Slide Coagglutination for Salmonella typhi Antigens in Broths Inoculated with Feces from Typhoid Fever Patients

    Science.gov (United States)

    1981-12-01

    SLIDE COAGGLUTINATION FOR SALMONELLA TYPHI ANTIGENS IN BROTHS INOCULATED WITH FECES FROM TYPHOID FEVER PATIENTS R. C. Rockhill, L. W. Rumans and M...permission of the Editor, Southeast Asian Journal of Tropical Medicine and Public Health SLIDE COAGGLUTINATION FOR SALMONELLA TYPHI ANTIGENS IN...525 Vol. 12 No. 4 December 1981 1 1P .. .. . --U- 1- "J SLIDE COAGGLUTINATION O Salmonella typhi ANTIGFNS the Infectious Disease Hospital and cultured

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

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    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.

  12. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa.

    Science.gov (United States)

    Feasey, Nicholas A; Dougan, Gordon; Kingsley, Robert A; Heyderman, Robert S; Gordon, Melita A

    2012-06-30

    Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20-25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission.

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

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    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.

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

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    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.

  15. Open study of short course Fleroxacin for Typhoid and Paratyphoid Fever

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    R. H.H. Nelwan

    2002-03-01

    Full Text Available The objective of this study was to evaluate clinical and bacteriological effect of short course fleroxacin in uncomplicated typhoid and paratyphoid fever patients. Four hundred mg of fleroxacin was given oraly once daily for a period of 3 to 5 days. The diagnosis of typhoid and paratyphoid fever was established by clinical picture as well as blood culture or Widal serology test. Thirty patients in whom the clinical picture was confirmed as a typhoid or paratyphoid infection were eligible for this investigation. They consisted of 15 males and 15 females ranging in age from 18-38 years average 27.5 years of whom 18 were diagnosed by blood culture consisting of 16 S.typhi positive cases and two S.paratyphi A, while 12 other cases were positively confirmed by serial Widal agglutination serology. These cases suffered from fever between 3-14 days with a minimum recorded body temperature elevation of 38.5 degrees Celsius. Clinical response with defervescence of fever was obtained in the positive blood culture group within 3 days (8 patients including 2 cases positive for S.paratyphi A and within two additional days (5 days in the remaining 10 cases. In the twelve cases with a positive serology for typhoid fever a clinical response was obtained for defervescence within 3 days (6 cases with 4 of these cases were on 3 days of fleroxacin and 2 cases on 5 days of fleroxacin. In the remaining 6 serologic positive cases fever resolved after 4-6 days with an average of 5 days with one on 3 days of fleroxacin and the rest (5 cases on 5 days of fleroxacin. All positive blood culture cases reverted to negative after the fleroxacin course. No relapse or carrier state was recorded in this serie. It may be concluded that a 3 to 5 days closely monitored course of fleroxacin has excellent clinical as well as bacteriological efficacy in noncomplicated typhoid and paratyphoid fever. (Med J Indones 2002; 11: 41-7Keywords: fluoroquinolones, enteric infections, short

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

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    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.

  17. Comparative study of immunochromatographic assay (IgM) and widal test for early diagnosis of typhoid fever.

    Science.gov (United States)

    Sultana, S; Hossain, M A; Alam, M A; Paul, S K; Kabir, M R; Hoque, S M; Yesmin, T; Habiba, U; Sarkar, S R; Maruf, M A; Halim, P I; Hoque, M R

    2012-10-01

    Typhoid fever is a severe systemic infection endemic in many developing countries, including Bangladesh. Present study evaluated immunochromatographic test (ICT) and Widal test in the early diagnosis of typhoid fever cases. The study was carried out in the department of Microbiology, Mymensingh Medical College, Mymensingh between July, 2010 and June, 2011, including 200 individuals of different age and sex. Of them, 150 were clinically suspected cases of typhoid fever and 50 age-sex matched controls. Among 150 blood samples from the suspected cases 106(70.7%) were positive for IgM of Salmonella typhi by ICT and 67(44.7%) were positive by Widal test. Whereas, among the 50 controls 4(8%) were positive by ICT and 6(12%) were positive by Widal test. The sensitivity, specificity, positive and negative predictive value of the ICT was found as 83.3%, 92.00%, 91.9% and 83.6% respectively. On the other hand corresponding values for Widal test were of 44.4%, 88%, 80% and 59.5% respectively. Thus, The ICT (IgM) is better alternative to Widal test for early and accurate diagnosis of typhoid fever. The ICT (IgM) is rapid, easy to perform, applicable for field use and highly sensitive and specific for detection of antibodies in patients with typhoid fever.

  18. Malaria, Typhoid Fever, and Their Coinfection among Febrile Patients at a Rural Health Center in Northwest Ethiopia: A Cross-Sectional Study

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    Meseret Birhanie

    2014-01-01

    Full Text Available Background. Malaria and typhoid fever are major public health problems in tropical and subtropical countries. People in endemic areas are at risk of contracting both infections concurrently. Objectives. The study was aimed at determining the prevalence and associated risk factors of malaria, typhoid, and their coinfection among febrile patients. Methods. A cross-sectional study was conducted on 200 febrile patients suspected for malaria and/or typhoid fever from April to May, 2013, at Ayinba Health Center, Northwest Ethiopia. Blood samples were collected for blood culture, Widal test, and blood film preparation. Data were analyzed using SPSS version 20 statistical software. Results. The prevalence of malaria was 36.5% (n=73. Among these 32 (43.8%, 30 (41.1% and 11 (15.1% were positive for P. falciparum, P. vivax, and mixed infections, respectively. The seroprevalence of typhoid fever was 38 (19%, but 1 (0.5% with blood culture. Malaria typhoid fever coinfection was 13 (6.5%. 2–5-year-old children and poor hand washing habit were significantly associated with malaria and typhoid infection, respectively (P<0.05. Conclusions. The prevalence of malaria and typhoid fever was found high. Further studies should be done on the other determinants of malaria and typhoid fever coinfection in different seasons and different study areas.

  19. Malaria, Typhoid Fever, and Their Coinfection among Febrile Patients at a Rural Health Center in Northwest Ethiopia: A Cross-Sectional Study.

    Science.gov (United States)

    Birhanie, Meseret; Tessema, Belay; Ferede, Getachew; Endris, Mengistu; Enawgaw, Bamlaku

    2014-01-01

    Background. Malaria and typhoid fever are major public health problems in tropical and subtropical countries. People in endemic areas are at risk of contracting both infections concurrently. Objectives. The study was aimed at determining the prevalence and associated risk factors of malaria, typhoid, and their coinfection among febrile patients. Methods. A cross-sectional study was conducted on 200 febrile patients suspected for malaria and/or typhoid fever from April to May, 2013, at Ayinba Health Center, Northwest Ethiopia. Blood samples were collected for blood culture, Widal test, and blood film preparation. Data were analyzed using SPSS version 20 statistical software. Results. The prevalence of malaria was 36.5% (n = 73). Among these 32 (43.8%), 30 (41.1%) and 11 (15.1%) were positive for P. falciparum, P. vivax, and mixed infections, respectively. The seroprevalence of typhoid fever was 38 (19%), but 1 (0.5%) with blood culture. Malaria typhoid fever coinfection was 13 (6.5%). 2-5-year-old children and poor hand washing habit were significantly associated with malaria and typhoid infection, respectively (P typhoid fever was found high. Further studies should be done on the other determinants of malaria and typhoid fever coinfection in different seasons and different study areas.

  20. High incidence of co-infection with Malaria and Typhoid in febrile HIV infected and AIDS patients in Ekpoma, Edo State, Nigeria.

    Science.gov (United States)

    Agwu, E; Ihongbe, J C; Okogun, G R A; Inyang, N J

    2009-04-01

    This survey was designed to determine the prevalence of Plasmodium falciparum and Salmonella Typhi among febrile HIV/AIDS patients in Ekpoma. Malaria and typhoid risk factors in Ekpoma included occupation, poor health facilities and poor sanitation. Malaria and typhoid are highly prevalent among Ekpoma HIV/AIDS patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chau, P.Y.; Tsang, R.S.W.; Lam, S.K. (Hong Kong Univ.); La Brooy, J.T.; Rowley, D. (Adelaide Univ. (Australia))

    1981-12-01

    Antibodies to the lipopolysaccharide (LPS) and protein antigens of S. typhi in secretions of small intestine obtained from 12 typhoid patients, four typhoid carriers and 16 non-typhoid control subjects were measured by a solid-phase radioimmunoassay technique using /sup 125/I labelled anti-immunoglobulin antibody. Intestinal secretions obtained from typhoid patients as a group had significantly higher anti-LPS and anti-protein antibodies than those from the control group. These antibodies were both IgM and IgA classes. There was no correlation between the IgM or IgA antibody levels in serum and those in the intestinal secretions. In the intestinal secretions obtained from typhoid carriers, on the other hand, only IgA-class antibodies to the LPS and protein antigens of S. typhi were present at high levels.

  2. Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.

    Science.gov (United States)

    Waddington, Claire S; Darton, Thomas C; Woodward, William E; Angus, Brian; Levine, Myron M; Pollard, Andrew J

    2014-05-01

    Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design.

  3. 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.

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

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    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.

  5. 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.

  6. Comparison between azithromycin and cefixime in the treatment of typhoid fever in children.

    Science.gov (United States)

    Begum, B; Haque, M A; Ahmed, M S; Islam, M N; Ahsan, M M; Khan, A H; Hasan, M M; Akhtaruzzaman, M; Hossain, M A; Khaleque, M A; Choudhury, A M; Khatun, A A

    2014-07-01

    An intervention study was carried out in the department of paediatrics of Mymensingh Medical College Hospital, Mymensingh to compare the clinical efficacy of Azithromycin in the treatment of childhood typhoid fever with that of cefixime for a period of one year from January 2011 to December 2011. A total of 60 cases of typhoid fever were enrolled in to a randomized clinical trial and was divided into two groups. The inclusion criteria of the cases were: Documented fever for more than 4 days plus two or more of the following clinical features: toxic physical appearance, intestinal complaints, coated tongue, ceacal gurgling, hepatomegaly and splenomegaly, diarrhoea and constipation plus positive Widal test and/or blood culture positivity. Patients who had complication like GIT heamorrhage; intestinal perforaion and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg/day for a period of 07 days Cefixime was given at a dose of 20mg/kg/day in two divided dose for 14 days. The mean time of defervesence was 4.05+1.14 days with azithromycin and 3.41+0.95 with cefixime respectively. The minimum defervesence time was 02 days and maximum defervesence time was 07 days. Clinical cure rate was 87% in azithromycin group and 93% in cefixime group. No serious adverse effect was noted related to azithromycin and cefixime therapy except nausea, vomiting, diarrhoea and jaundice. It was found that azithromycin is almost as effective as cefixime in the treatment of typhoid fever.

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

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    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. Waterborne typhoid fever in Dade County, Florida. Clinical and therapeutic evaluation of 105 bacteremic patients.

    Science.gov (United States)

    Hoffman, T A; Ruiz, C J; Counts, G W; Sachs, J M; Nitzkin, J L

    1975-10-01

    An extensive outbreak of waterborne typhoid fever occurred in 1973 at a migrant labor camp in Dade County, Florida. Blood cultures from 105 of the 188 patients with proved or presumptive cases of typhoid fever grew Salmonella typhi. The clinical and laboratory findings in these patients were reviewed. Fever, usually with temperatures above 38.8 degrees C and of the sustained type, was a primary manifestation of disease, although a majority of the patients also complained of headache and gastroenteric symptoms. Hepatic or splenic enlargement was present in 52 per cent and 42 per cent, respectively, whereas rose spots were detected in only 13 per cent. The total leukocyte count was normal in 74 per cent, but serum levels of liver and muscle enzymes were frequently elevated. Gastrointestinal, pulmonary and neurologic complications were infrequent; circulatory failure was not observed. Defervescence in response to antibiotic therapy was variable; however, the median response among 68 patients who received chloramphenicol was two days less than that in 34 patients treated with ampicillin. There was one possible treatment failure with ampicillin. The relapse rate of 10 per cent in chloramphenicol-treated patients was not significantly greater than the 3 per cent rate among those treated with ampicillin. Serologic studies for typhoid fever were of limited diagnostic value since the titer of agglutinins was 1:160 or higher in 49 per cent of the serums obtained before treatment, and a fourfold rise in titer occurred in only 24 per cent of 57 patients studied. The serologic response to chloramphenicol treatment did not differ from that to ampicillin.

  9. 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...

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, R.S.W.; Chau, P.Y.; Lam, S.K. (Hong Kong Univ.); La Brooy, J.T.; Rowley, D. (Adelaide Univ. (Australia))

    1981-12-01

    Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique with /sup 125/I labelled anti-immunoglobulin antibody. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed.

  12. 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.

  13. 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.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.

  14. 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.

  15. Increase in isolation of extended spectrum beta lactamase producing multidrug resistant non typhoidal Salmonellae in Pakistan

    Directory of Open Access Journals (Sweden)

    Khan Erum

    2010-04-01

    Full Text Available Abstract Background Increasing resistance to quinolones and ceftriaxone in non typhoidal Salmonellae is a global concern. Resistance to quinolone and 3rd generation cephalosporin amongst non typhoidal Salmonellae (NTS from Pakistan has been reported in this study. Methods Retrospective analysis of laboratory data was conducted (1990-2006. NTS were isolated and identified from clinical samples using standard microbiological techniques. Antimicrobial susceptibility testing was performed by Kirby Bauer. Extended spectrum beta lactamase production (ESBL was detected using combined disc method. Ciprofloxacin sensitivity was detected by nalidixic acid screening method. Minimum inhibitory concentration (MIC of ciprofloxacin was determined by agar dilution method. Statistical analysis was performed using SPSS version 13. Results Analysis of 1967 NTS isolates showed a significant increase in ciprofloxacin resistance from 23% in 2002 to 50.5% in 2006, with increased mean MIC values from 0.6 to 1.3 ug/mL. Ceftriaxone resistant NTS also increased and ESBL production was seen in 98.7% isolates. These isolates exhibited high resistance against amoxicillin clavulanic acid (57%, gentamicin (69%, amikacin (44% and piperacillin tazobactam (30%. No resistance to carbapenem was seen. Ceftriaxone resistance was significantly higher in children Conclusions Increase in quinolone and ceftriaxone NTS is a serious threat to public health requiring continuous surveillance and use of appropriate screening tests for laboratory detection.

  16. Clean hands: prevention of typhoid fever in rural communities in Egypt.

    Science.gov (United States)

    Lohiniva, Anna L; Saeed, Mohamed; El-Sayeed, Nasr; Talaat, Maha

    Typhoid fever is a serious public health problem in Egypt. Effective prevention strategies include the promotion of handwashing. This study explores factors that influence handwashing practices in the Egyptian setting and makes recommendations on how to use this information in a handwashing campaign. In addition to key informant interviews, 16 focus group discussions and 21 in-depth interviews were carried out with female respondents in three different rural sites. The data was analyzed by using content analysis technique. The findings showed that the concept of dirt (microbaat and talaus) influences hygiene behavior as it relates to the outside (i.e., real and visible things). The respondents have low risk perceptions related to typhoid fever and they do not conceptualize long disease transmission chains. The scarcity of water and problems with disposal of waste water hinder handwashing. These findings were incorporated into a pilot campaign to promote handwashing using strategies that included the visualization of germs in critical areas during critical times, discussions of germ theory, and encouragement to solve environmental and infrastructural constraints that hinder handwashing practices at the household level.

  17. 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.

  18. 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.

  19. Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea using a composite reference standard.

    Science.gov (United States)

    Siba, Valentine; Horwood, Paul F; Vanuga, Kilagi; Wapling, Johanna; Sehuko, Rebecca; Siba, Peter M; Greenhill, Andrew R

    2012-11-01

    Typhoid fever remains a major global health problem. A major impediment to improving outcomes is the lack of appropriate diagnostic tools, which have not significantly improved in low-income settings for 100 years. We evaluated two commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously reported high-burden area of Papua New Guinea. Samples were collected from 530 outpatients with axillary temperatures of ≥37.5°C, and analysis was conducted on all malaria-negative samples (n = 500). A composite reference standard of blood culture and PCR was used, by which 47 participants (9.4%) were considered typhoid fever positive. The sensitivity and specificity of the Tubex (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively) tests were not high enough to warrant their ongoing use in this setting; however, the sensitivity and specificity for the TR-02 prototype were promising (89.4% and 85.0%, respectively). An axillary temperature of ≥38.5°C correlated with typhoid fever (P = 0.014). With an appropriate diagnostic test, conducting typhoid fever diagnosis only on patients with high-grade fever could dramatically decrease the costs associated with diagnosis while having no detrimental impact on the ability to accurately diagnose the illness.

  20. "In the Fall of the Year We Were Troubled with Some Sickness": Typhoid Fever Deaths, Sherman Institute, 1904.

    Science.gov (United States)

    Keller, Jean A.

    1999-01-01

    Driven by his vision of the ideal American Indian vocational boarding school, Harwood Hall, an experienced administrator of Indian boarding schools, lobbied Congress to build Sherman Institute, which opened in Riverside, California, in 1902. A master of public relations, Hall downplayed the illness and deaths of students when typhoid fever swept…

  1. 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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  5. Histopathological analysis of Salmonella chronic carriage in the mouse hepatopancreatobiliary system.

    Directory of Open Access Journals (Sweden)

    Geoffrey Gonzalez-Escobedo

    Full Text Available Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected. However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.

  6. Systemic and extraintestinal forms of human infection due to non-typhoid salmonellae in Bulgaria, 2005-2010.

    Science.gov (United States)

    Asseva, G; Petrov, P; Ivanova, K; Kantardjiev, T

    2012-11-01

    The purpose of this investigation was to review the clinical cases diagnosed as systemic or extraintestinal salmonellosis between 2005 and 2010 in Bulgaria, to determine the antimicrobial resistance of the causative salmonellae, and to analyze the pulsed field gel electrophoresis (PFGE) profiles of extraintestinal Salmonella Corvallis isolates. Culture, biochemical tests, and serotyping were performed. Resistance to 12 antimicrobial agents was studied with the Bauer-Kirby disk diffusion method. The double-disk synergy method was used for the screening of the presence of extended-spectrum beta-lactamases (ESBLs). PFGE typing and analysis of the dendrogram was performed for the comparative investigation of Salmonella Corvallis isolates. Between 2005 and 2010, 2,227 human non-typhoid Salmonella isolates were investigated at the National Reference Laboratory of Enteric Pathogens, Sofia, Bulgaria. Thirty-three strains (1.48 %) from nine national regions were isolated from patients with systemic and extraintestinal forms of salmonellosis. The serotype distribution was as follows: S. enteritidis (n = 21), S. choleraesuis (diphasic n = 3; monophasic n = 3), S. typhimurium (n = 2), Salmonella Corvallis (n = 2), Salmonella Montevideo (n = 1), and S. javiana (n = 1). Eight patients developed severe forms of infections: sepsis (n = 2), septic shock (n = 1 with fatal outcome), meningitis (n = 3), and acute renal failure (n = 2). Twenty-two percent of isolates were resistant to ampicillin and gentamicin, 17.64 % to tetracycline, 14.28 % to nalidixic acid, and 10 % to chloramphenicol. All isolates were susceptible to ciprofloxacin. One Salmonella Corvallis isolate recovered from a patient with chronic hemolytic anemia produced an ESBL and its PFGE profile demonstrated less than 96 % similarity to fecal and wound Salmonella Corvallis with susceptible phenotypes. S. enteritidis was the most common cause of systemic and

  7. 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.

  8. 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

  9. Clinical outcomes in typhoid fever: adverse impact of infection with nalidixic acid-resistant Salmonella typhi

    Directory of Open Access Journals (Sweden)

    Kabra SK

    2005-05-01

    Full Text Available Abstract Background Widespread use of fluoroquinolones has resulted in emergence of Salmonella typhi strains with decreased susceptibility to fluoroquinolones. These strains are identifiable by their nalidixic acid-resistance. We studied the impact of infection with nalidixic acid-resistant S. typhi (NARST on clinical outcomes in patients with bacteriologically-confirmed typhoid fever. Methods Clinical and laboratory features, fever clearance time and complications were prospectively studied in patients with blood culture-proven typhoid fever, treated at a tertiary care hospital in north India, during the period from November 2001 to October 2003. Susceptibility to amoxycillin, co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone were tested by disc diffusion method. Minimum inhibitory concentrations (MIC of ciprofloxacin and ceftriaxone were determined by E-test method. Results During a two-year period, 60 patients (age [mean ± SD]: 15 ± 9 years; males: 40 [67%] were studied. All isolates were sensitive to ciprofloxacin and ceftriaxone by disc diffusion and MIC breakpoints. However, 11 patients had clinical failure of fluoroquinolone therapy. Infections with NARST isolates (47 [78%] were significantly associated with longer duration of fever at presentation (median [IQR] 10 [7-15] vs. 4 [3-6] days; P = 0.000, higher frequency of hepatomegaly (57% vs. 15%; P = 0.021, higher levels of aspartate aminotransferase (121 [66–235] vs. 73 [44–119] IU/L; P = 0.033, and increased MIC of ciprofloxacin (0.37 ± 0.21 vs. 0.17 ± 0.14 μg/mL; P = 0.005, as compared to infections with nalidixic acid-susceptible isolates. All 11 patients with complications were infected with NARST isolates. Total duration of illness was significantly longer in patients who developed complications than in patients who did not (22 [14.8–32] vs. 12 [9.3–20.3] days; P = 0.011. Duration of prior antibiotic intake had a strong positive correlation with the

  10. Clinical outcomes in typhoid fever: adverse impact of infection with nalidixic acid-resistant Salmonella typhi

    Science.gov (United States)

    Kadhiravan, Tamilarasu; Wig, Naveet; Kapil, Arti; Kabra, SK; Renuka, K; Misra, Anoop

    2005-01-01

    Background Widespread use of fluoroquinolones has resulted in emergence of Salmonella typhi strains with decreased susceptibility to fluoroquinolones. These strains are identifiable by their nalidixic acid-resistance. We studied the impact of infection with nalidixic acid-resistant S. typhi (NARST) on clinical outcomes in patients with bacteriologically-confirmed typhoid fever. Methods Clinical and laboratory features, fever clearance time and complications were prospectively studied in patients with blood culture-proven typhoid fever, treated at a tertiary care hospital in north India, during the period from November 2001 to October 2003. Susceptibility to amoxycillin, co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone were tested by disc diffusion method. Minimum inhibitory concentrations (MIC) of ciprofloxacin and ceftriaxone were determined by E-test method. Results During a two-year period, 60 patients (age [mean ± SD]: 15 ± 9 years; males: 40 [67%]) were studied. All isolates were sensitive to ciprofloxacin and ceftriaxone by disc diffusion and MIC breakpoints. However, 11 patients had clinical failure of fluoroquinolone therapy. Infections with NARST isolates (47 [78%]) were significantly associated with longer duration of fever at presentation (median [IQR] 10 [7-15] vs. 4 [3-6] days; P = 0.000), higher frequency of hepatomegaly (57% vs. 15%; P = 0.021), higher levels of aspartate aminotransferase (121 [66–235] vs. 73 [44–119] IU/L; P = 0.033), and increased MIC of ciprofloxacin (0.37 ± 0.21 vs. 0.17 ± 0.14 μg/mL; P = 0.005), as compared to infections with nalidixic acid-susceptible isolates. All 11 patients with complications were infected with NARST isolates. Total duration of illness was significantly longer in patients who developed complications than in patients who did not (22 [14.8–32] vs. 12 [9.3–20.3] days; P = 0.011). Duration of prior antibiotic intake had a strong positive correlation with the duration of fever at

  11. 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

  12. A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

    OpenAIRE

    Christiane Dolecek; Thi Phi La Tran; Ngoc Rang Nguyen; Thi Phuong Le; Vinh Ha; Quoc Tuan Phung; Cong Du Doan; Thi Be Bay Nguyen; Thanh Long Duong; Bich Ha Luong; Trung Binh Nguyen; Thi Anh Hong Nguyen; Ngoc Dung Pham; Ngoc Lanh Mai; Van Be Bay Phan

    2008-01-01

    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 op...

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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

  17. 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.

  18. Plasmid-mediated quinolone resistance in typhoidal Salmonellae: A preliminary report from South India

    Directory of Open Access Journals (Sweden)

    V K Geetha

    2014-01-01

    Full Text Available Background: Fluoroquinolones are the drugs extensively employed for the treatment of Salmonella infections. Over the couple of decades that have elapsed since the introduction of fluoroquinolones, resistance to these agents by Enterobacteriaceae family members has become common and widespread. Although fluoroquinolone resistance is mediated by genomic DNA (deoxyribonucleic acid as well as plasmid DNA, the plasmid-mediated quinolone resistance (PMQR facilitates higher level resistance by interacting with genomic mechanism and is capable of horizontal spread. Materials and Methods: During a period of 1-year, 63 typhoidal Salmonellae were isolated from 14,050 blood cultures and one parietal wall abscess. 36 (56.25% were Salmonella Typhi and 27 (42% were Salmonella Paratyphi A. They were all screened for resistance by the disc diffusion method and their minimum inhibitory concentrations were determined using agar dilution, broth dilution and E-strip method. Ciprofloxacin resistant isolates were screened for PMQR determinants by polymerase chain reaction assay. Results: All the 63 isolates were resistant to nalidixic acid. Among the 36 S. Typhi isolates 20 were resistant to ciprofloxacin, of which 14 carried the plasmid gene qnrB and one carried the aac(6′-Ib-cr gene. qnrA and qnrS genes were not detected. Ciprofloxacin resistance was not seen in any of the S. Paratyphi A isolates. Conclusion: The antibiotic sensitivity pattern of typhoidal Salmonellae shows an increasing trend of PMQR. The allele B of qnr gene was found to be the predominant cause of PMQR in this study.

  19. Typhoidal Salmonellae: Use of Multi-Locus Sequence Typing to Determine Population Structure.

    Science.gov (United States)

    Sharma, Priyanka; Dahiya, Sushila; Balaji, Veeraraghavan; Kanga, Anil; Panda, Preetilata; Das, Rashna; Dhanraju, Anbumani; Mendiratta, Deepak Kumar; Sood, Seema; Das, Bimal Kumar; Kapil, Arti

    2016-01-01

    Enteric fever is an invasive infection predominantly caused by Salmonella enterica serovars Typhi and Paratyphi A. The pathogens have evolved from other nontyphoidal salmonellaeto become invasive and host restricted. Emergence of antimicrobial resistance in typhoidal salmonellae in some countries is a major therapeutic concern as the travelers returning from endemic countries carry resistant strains to non endemic areas. In order to understand the epidemiology and to design disease control strategies molecular typing of the pathogen is very important. We performed Multilocus Sequence Typing (MLST) of 251 S. Typhi and 18 S. Paratyphi strains isolated from enteric fever patients from seven centers across India during 2010-2013to determine the population structure and prevalence of MLST sequence types in India. MLST analysis revealed the presence of five sequence types (STs) of typhoidal salmonellae in India namely ST1, ST2 and ST3 for S. Typhi and ST85 and ST129 for S. Paratyphi A.S. Typhi strains showed monophyletic lineage and clustered in to 3 Sequence Types-ST1, ST2 and ST3 and S. Paratyphi A isolates segregated in two sequence types ST85 and ST129 respectively. No association was found between antimicrobial susceptibility and sequence types. This study found ST1 as the most prevalent sequence type of S. Typhi in India followed by ST2, which is in concordance with previous studies and MLST database. In addition a rare sequence type ST3 has been found which is reported for the first time from the Indian subcontinent. Amongst S. Paratyphi A, the most common sequence type is ST129 as also reported from other parts of world. This distribution and prevalence suggest the common spread of the sequence types across the globe and these findings can help in understanding the disease distribution.

  20. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... alcohol abuse over many years. Repeated episodes of acute ... chronic pancreatitis. Genetics may be a factor in some cases. ...

  1. [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.

  2. Typhoid fever

    Science.gov (United States)

    ... most commonly caused due to a bacteria called Salmonella typhi ( S typhi ). Causes S typhi is spread through contaminated food, ... as food handlers. Alternative Names Enteric fever Images Salmonella typhi organism Fly Digestive system organs References Harris JB, ...

  3. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis

    OpenAIRE

    Malfait, A. M.; Gallily, R; Sumariwalla, P. F.; Malik, A. S.; Andreakos, E; Mechoulam, R.; Feldmann, M

    2000-01-01

    The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA). CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete Freund's adjuvant. The CII used was either bovine or murine, resulting in classical acute CIA or in chronic relapsing CIA, respectively. CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked pro...

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

    Directory of Open Access Journals (Sweden)

    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

  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. Refractory hypocalcemia precipitated by dual infection with typhoid fever and hepatitis A in a patient with congenital hypoparathyroidism

    Institute of Scientific and Technical Information of China (English)

    Suman S Karanth; Ram Bhat; Anurag Gupta

    2012-01-01

    We present this rare occurrence of a17 yr old boy, a known case of congenital hypoparathyroidism, who presented with fever and jaundice for8 days and2 episodes of generalised tonic-clonic seizures.Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels.Investigations revealed severe hypocalcaemia(3.2 mg/dL), low25 hydroxyvitamin D levels and hypomagnesaemia.The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes.Microbiological investigations were confirmatory for both hepatitis A and typhoid fever.In spite of the aggressive management with intravenous calcium gluconate infusion, refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels.We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient.

  7. Epidemiology, clinical manifestations, and molecular typing of salmonella typhi isolated from patients with typhoid fever in Lebanon.

    Science.gov (United States)

    Kanj, Souha S; Kanafani, Zeina A; Shehab, Marwa; Sidani, Nisreen; Baban, Tania; Baltajian, Kedak; Dakdouki, Ghenwa K; Zaatari, Mohamad; Araj, George F; Wakim, Rima Hanna; Dbaibo, Ghassan; Matar, Ghassan M

    2015-06-01

    The objective of this study was to examine the epidemiology and the clinical manifestations of typhoid fever as well as the susceptibility and strain relatedness of Salmonella typhi isolates in Lebanon from 2006 to 2007. A total of 120 patients with typhoid fever were initially identified from various areas of the country based on positive culture results for S. typhi from blood, urine, stools, bone marrow and/or positive serology. Clinical, microbiological and molecular analysis was performed on cases with complete data available. These results indicated that drinking water was an unlikely mode of transmission of the infection. Despite increasing reports of antimicrobial resistance among S. typhi isolates, the vast majority of these isolates were susceptible to various antibiotic agents, including ampicillin, cephalosporins, quinolones, and trimethoprim/sulfamethoxazole. Molecular analysis of the isolates revealed a predominance of one single genotype with no variation in distribution across the geographical regions.

  8. 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.

  9. Effect of D-pinitol on the TGF-β1 expression in a murine model of chronic asthma%D-松醇对慢性哮喘小鼠模型肺组织转化生长因子β1表达的影响

    Institute of Scientific and Technical Information of China (English)

    顾晓燕; 王毓薇; 蒋德升; 杜强

    2012-01-01

    目的:观察D-松醇对慢性哮喘小鼠模型转化生长因子(TGF-β1)的影响.方法:18只BALB/c小鼠按随机原则分成正常对照组、哮喘模型组、D-松醇干预组,每组6只,末次抗原激发24h后,检测各组小鼠的肺功能,HE染色观察气道炎症变化;Masson三色染色观察气道纤维化的改变;real-time PCR观察肺组织TGF-β1 mRNA的表达;采用ELISA观察支气管肺泡灌洗液中TGF-β1的表达.结果:哮喘模型组小鼠气道炎症、气道高反应性和气道重塑明显加重,而D-松醇能显著抑制慢性哮喘模型小鼠的气道炎症和气道高反应性,且D-松醇干预后哮喘模型小鼠肺组织TGF-β1 mRNA和肺泡灌洗液中TGF-β1表达也显著降低.结论:D-松醇能抑制慢性哮喘模型小鼠的气道重塑,其机制可能通过抑制肺组织TGF-β1的表达而实现.%Objective:To observe the effect of D-pinitol on the expression of transforming growth factor-β1 (TGF-β1) in a murine model of chronic asthma. Methods: Eighteen BALB/c mice were randomly divided into 3 groups,namely control group,OVA group and D-pinitol group. Pulmonary function was measured to evaluate the resistance of expiration 24 hours after the last OVA challenge, hematoxylin and eosin (HE) staining was used to assess the inflammatory cell infiltrates,and Masson's trichrome to determine airway fibrosis. Hie expression of TGF-β1 Mrna in lung was measured by real-time PCR. The concentration of TGF-β1 in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunoabsorbent assay (ELISA). Results: All the parameters associated with airway inflammation,airway hyperresponsiveness (AHR) and remodeling were increased in the OVA group,and decreased by treatment of D-pinitol(P < 0.0S). Treatment with D-pinitol significantly inhibited the levels of TGF-β1 in the lung tissue and in the BALF (P < 0.05). Conclusion: These data demonstrated that D-pinitol could suppress the progression of airway remodeling in a

  10. 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.

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

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    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.

  12. Sexual transmission of Trypanosoma cruzi in murine model.

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    Ribeiro, Marcelle; Nitz, Nadjar; Santana, Camilla; Moraes, Aline; Hagström, Luciana; Andrade, Rafael; Rios, Adriano; Sousa, Alessandro; Dallago, Bruno; Gurgel-Gonçalves, Rodrigo; Hecht, Mariana

    2016-03-01

    Trypanosoma cruzi is mainly transmitted by blood-sucking triatomines, but other routes also have epidemiological importance, such as blood transfusion and congenital transmission. Although the possibility of sexual transmission of T. cruzi has been suggested since its discovery, few studies have been published on this subject. We investigated acquisition of T. cruzi by sexual intercourse in an experimental murine model. Male and female mice in the chronic phase of Chagas disease were mated with naive partners. Parasitological, serological and molecular tests demonstrated the parasites in tissues and blood of partners. These results confirm the sexual transmission of T. cruzi in mice.

  13. Diagnostic imaging advances in murine models of colitis.

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    Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

    2016-01-21

    Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.

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

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    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.

  15. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia.

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    Bhuvanendran, Saatheeyavaane; Hussin, Hani M; Meran, Lila P; Anthony, Amy A; Zhang, Leilei; Burch, Lauranell H; Phua, Kia K; Ismail, Asma; Balaram, Prabha

    2011-09-01

    Typhoid fever is a major health problem with frequent outbreaks in Kelantan, Malaysia. Prevalence of TLR4 gene polymorphisms varies with ethnic groups (0-20%) and predisposean individual to gram-negative infections. The prevalence rate of TLR4 Asp299Gly and Thr399lle polymorphisms in the Malay population or the influence of these on typhoid fever susceptibility is not yet reported. 250 normal and 304 susceptible Malay individuals were investigated for these polymorphisms using allele-specific PCR and analysed for its association with typhoid fever susceptibility. The total prevalence of polymorphisms in the normal population was 4.8% in comparison to 12.5% in the susceptible population (p = 0.002). An increased frequency of both polymorphisms was observed in the susceptible population (p population and suggests that these polymorphisms confer a higher risk for typhoid, infection. The higher incidence of typhoid fever in Kelantan could be attributed to the higher percentage of Malays (95%) in this state. In order to reduce the incidence of this disease, people with these polymorphisms, can be prioritised for prophylactic strategies.

  16. 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

  17. Evaluation of the Widal tube agglutination test for the diagnosis of typhoid fever among children admitted to a rural hdospital in Tanzania and a comparison with previous studies

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    Malahiyo Rajabu

    2010-06-01

    Full Text Available Abstract Background The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi. However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. Methods We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." Results We found that 16 (1% of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. Conclusion Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of ≥ 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.

  18. 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.

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

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    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

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

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    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.

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

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    Zhang, Xingyu; Liu, Yuanyuan; Yang, Min; Zhang, Tao; Young, Alistair A; Li, Xiaosong

    2013-01-01

    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.

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

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    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.

  3. 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.

  4. Resistance Patterns of Typhoid Fever in Children: A Longitudinal Community-Based Study.

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    Vala, Snehal; Shah, Urvesh; Ahmad, Syed Amir; Scolnik, Dennis; Glatstein, Miguel

    2016-01-01

    Salmonella typhi and S. paratyphi are important causes of bacteremia in children, especially those from the developing world. There is a lack of standardized treatment protocols for such patients in the literature, and there are also reports of therapeutic failure related to resistance to commonly used antibiotics. We analyzed the epidemiological, clinical, and antimicrobiological sensitivity patterns of disease in patients diagnosed with blood culture-positive typhoid fever over a 6-month period in a tertiary-care pediatric hospital in western India. Data were retrospectively analyzed for all patients with Salmonella isolates on blood culture between January 1 and June 30, 2011 at the Synergy Neonatal and Pediatric Hospital. Susceptibility of isolates to antimicrobials and minimum inhibitory concentrations were determined. Demographic data, symptoms and signs, basic laboratory results, treatment courses, and clinical outcomes were collected from clinical charts. All of the 61 isolates of S. typhi were sensitive to cefepime (fourth-generation cephalosporin), 96% to third-generation cephalosporins, and 95% to quinolones. There was intermediate sensitivity to ampicillin (92%) and chloramphenicol (80%). Notably, azithromycin resistance was observed in 63% of isolates. All patients ultimately made full recoveries. There is an urgent need for large scale, community-based clinical trials to evaluate the effectiveness of different antibiotics in enteric fever. Our antimicrobial susceptibility data suggest that quinolones and third-generation cephalosporins should be used as first-line antimicrobials in enteric fever. Although fourth-generation cephalosporins are useful, we feel their use should be restricted to complicated or resistant cases.

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

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    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.

  6. Genome dynamics and evolution of Salmonella Typhi strains from the typhoid-endemic zones.

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    Baddam, Ramani; Kumar, Narender; Shaik, Sabiha; Lankapalli, Aditya Kumar; Ahmed, Niyaz

    2014-12-12

    Typhoid fever poses significant burden on healthcare systems in Southeast Asia and other endemic countries. Several epidemiological and genomic studies have attributed pseudogenisation to be the major driving force for the evolution of Salmonella Typhi although its real potential remains elusive. In the present study, we analyzed genomes of S. Typhi from different parts of Southeast Asia and Oceania, comprising of isolates from outbreak, sporadic and carrier cases. The genomes showed high genetic relatedness with limited opportunity for gene acquisition as evident from pan-genome structure. Given that pseudogenisation is an active process in S. Typhi, we further investigated core and pan-genome profiles of functional and pseudogenes separately. We observed a decline in core functional gene content and a significant increase in accessory pseudogene content. Upon functional classification, genes encoding metabolic functions formed a major constituent of pseudogenes as well as core functional gene clusters with SNPs. Further, an in-depth analysis of accessory pseudogene content revealed the existence of heterogeneous complements of functional and pseudogenes among the strains. In addition, these polymorphic genes were also enriched in metabolism related functions. Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S. Typhi possibly resorts to metabolic fine tuning for its adaptation.

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

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    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.

  8. 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.

  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

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    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. Importance of Salmonella Typhi-Responsive CD8+ T Cell Immunity in a Human Typhoid Fever Challenge Model.

    Science.gov (United States)

    Fresnay, Stephanie; McArthur, Monica A; 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

    2017-01-01

    Typhoid fever, caused by the human-restricted organism Salmonella enterica serovar Typhi (S. Typhi), constitutes a major global health problem. The development of improved attenuated vaccines is pressing, but delayed by the lack of appropriate preclinical models. Herein, we report that high levels of S. Typhi-responsive CD8+ T cells at baseline significantly correlate with an increased risk of disease in humans challenged with a high dose (~10(4) CFU) wild-type S. Typhi. Typhoid fever development was associated with higher multifunctional S. Typhi-responsive CD8+ T effector memory cells at baseline. Early decreases of these cells in circulation following challenge were observed in both S. Typhi-responsive integrin α4β7- and integrin α4β7+ CD8+ T effector memory (TEM) cells, suggesting their potential to home to both mucosal and extra-intestinal sites. Participants with higher baseline levels of S. Typhi-responsive CD8+ T memory cells had a higher risk of acquiring disease, but among those who acquired disease, those with a higher baseline responses took longer to develop disease. In contrast, protection against disease was associated with low or absent S. Typhi-responsive T cells at baseline and no changes in circulation following challenge. These data highlight the importance of pre-existing S. Typhi-responsive immunity in predicting clinical outcome following infection with wild-type S. Typhi and provide novel insights into the complex mechanisms involved in protective immunity to natural infection in a stringent human model with a high challenge dose. They also contribute important information on the immunological responses to be assessed in the appraisal and selection of new generation typhoid vaccines.

  11. Importance of Salmonella Typhi-Responsive CD8+ T Cell Immunity in a Human Typhoid Fever Challenge Model

    Science.gov (United States)

    Fresnay, Stephanie; McArthur, Monica A.; 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.

    2017-01-01

    Typhoid fever, caused by the human-restricted organism Salmonella enterica serovar Typhi (S. Typhi), constitutes a major global health problem. The development of improved attenuated vaccines is pressing, but delayed by the lack of appropriate preclinical models. Herein, we report that high levels of S. Typhi-responsive CD8+ T cells at baseline significantly correlate with an increased risk of disease in humans challenged with a high dose (~104 CFU) wild-type S. Typhi. Typhoid fever development was associated with higher multifunctional S. Typhi-responsive CD8+ T effector memory cells at baseline. Early decreases of these cells in circulation following challenge were observed in both S. Typhi-responsive integrin α4β7− and integrin α4β7+ CD8+ T effector memory (TEM) cells, suggesting their potential to home to both mucosal and extra-intestinal sites. Participants with higher baseline levels of S. Typhi-responsive CD8+ T memory cells had a higher risk of acquiring disease, but among those who acquired disease, those with a higher baseline responses took longer to develop disease. In contrast, protection against disease was associated with low or absent S. Typhi-responsive T cells at baseline and no changes in circulation following challenge. These data highlight the importance of pre-existing S. Typhi-responsive immunity in predicting clinical outcome following infection with wild-type S. Typhi and provide novel insights into the complex mechanisms involved in protective immunity to natural infection in a stringent human model with a high challenge dose. They also contribute important information on the immunological responses to be assessed in the appraisal and selection of new generation typhoid vaccines. PMID:28303138

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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

    2016-06-17

    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.

  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.

  18. 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.

  19. 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.

  20. 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.

  1. Draft Genome Sequence of Salmonella enterica Serovar Typhi IMR_TP298/15, a Strain with Intermediate Susceptibility to Ciprofloxacin, Isolated from a Typhoid Outbreak

    Science.gov (United States)

    Hii, Shirley Yi Fen; Hashim, Rohaidah

    2017-01-01

    ABSTRACT Salmonella enterica serovar Typhi with reduced susceptibility to ciprofloxacin is increasingly being reported globally. An outbreak caused by Salmonella Typhi with decreased ciprofloxacin susceptibility has not been reported before in Malaysia. We present here the annotated draft genome of a Salmonella Typhi strain involved in a typhoid outbreak. PMID:28254988

  2. 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

  3. Draft Genome Sequence of Salmonellaenterica Serovar Typhi IMR_TP298/15, a Strain with Intermediate Susceptibility to Ciprofloxacin, Isolated from a Typhoid Outbreak.

    Science.gov (United States)

    Ahmad, Norazah; Hii, Shirley Yi Fen; Hashim, Rohaidah; Issa, Rahizan

    2017-03-02

    Salmonella enterica serovar Typhi with reduced susceptibility to ciprofloxacin is increasingly being reported globally. An outbreak caused by Salmonella Typhi with decreased ciprofloxacin susceptibility has not been reported before in Malaysia. We present here the annotated draft genome of a Salmonella Typhi strain involved in a typhoid outbreak.

  4. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    OpenAIRE

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of C...

  5. 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......, 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...

  6. 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.

  7. Flow cytometry of murine spermatocytes.

    Science.gov (United States)

    Gaysinskaya, Valeriya; Bortvin, Alex

    2015-04-01

    Protocols for purification of murine male germ cells by FACS based on Hoechst 33342 (Ho342) dye staining have been reported and optimized. However, the protocols are often challenging to follow, partly due to difficulties related to sample preparation, instrument parameters, data display, and selection strategies. In addition, troubleshooting of flow cytometry experiments usually requires some fluency in technical principles and instrument specifications and settings. This unit describes setup and procedures for analysis and sorting of male meiotic prophase I (MPI) cells and other germ cells. Included are procedures that guide data acquisition, display, gating, and back-gating critical for optimal data visualization and cell sorting. Additionally, a flow cytometry analysis of spermatogenesis-defective testis is provided to illustrate the applicability of the technique to the characterization and purification of cells from mutant testis.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  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. Role of T3SS-1 SipD Protein in Protecting Mice against Non-typhoidal Salmonella Typhimurium

    Science.gov (United States)

    Jneid, Bakhos; Moreau, Karine; Plaisance, Marc; Rouaix, Audrey; Dano, Julie

    2016-01-01

    Background Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine. Principal Findings We investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant. Conclusions and Significance Salmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for

  13. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  14. Household water treatment uptake during a public health response to a large typhoid fever outbreak in Harare, Zimbabwe.

    Science.gov (United States)

    Imanishi, Maho; Kweza, Patience F; Slayton, Rachel B; Urayai, Tanaka; Ziro, Odrie; Mushayi, Wellington; Francis-Chizororo, Monica; Kuonza, Lazarus R; Ayers, Tracy; Freeman, Molly M; Govore, Emmaculate; Duri, Clemence; Chonzi, Prosper; Mtapuri-Zinyowera, Sekesai; Manangazira, Portia; Kilmarx, Peter H; Mintz, Eric; Lantagne, Daniele

    2014-05-01

    Locally manufactured sodium hypochlorite (chlorine) solution has been sold in Zimbabwe since 2010. During October 1, 2011-April 30, 2012, 4,181 suspected and 52 confirmed cases of typhoid fever were identified in Harare. In response to this outbreak, chlorine tablets were distributed. To evaluate household water treatment uptake, we conducted a survey and water quality testing in 458 randomly selected households in two suburbs most affected by the outbreak. Although 75% of households were aware of chlorine solution and 85% received chlorine tablets, only 18% had reportedly treated stored water and had the recommended protective level of free chlorine residuals. Water treatment was more common among households that reported water treatment before the outbreak, and those that received free tablets during the outbreak (P 0.05). Outbreak response did not build on pre-existing prevention programs.

  15. 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

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

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    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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

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

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    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

  4. Apoptosis in irradiated murine tumors.

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    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.

  5. The typhoid and paratyphoid fever prevention research 60 years in Guangxi%广西伤寒及副伤寒防治研究60年

    Institute of Scientific and Technical Information of China (English)

    马小垒; 黄亚铭

    2014-01-01

    广西是全国伤寒及副伤寒流行较严重的省份之一,全年均有伤寒副伤寒病例出现,但1996年以前全区以伤寒流行为主,伤寒病例每年7~10月出现一个流行高峰期。自从1996年发现有副伤寒流行以来,到1999年的监测发现全年出现两个流行高峰期,分别是5月份的甲型副伤寒和10月份的伤寒各一个高峰期。而在2004年-2010年的监测发现两个高峰期时间非常接近,分别在7月和8月。广西从上世纪五十年代到九十年代中期伤寒的人群发病率分别为3.96/10万、8.83/10万、3.55/10万、5.04/10万和9.74/10万。1993年-2002年年均发病率为10.27/10万。2004年-2010年伤寒发病率波动在1.61/10万~5.41/10万之间,甲型副伤寒波动在0.80/10万~4.78/10万之间。目前广西的伤寒及副伤寒得到有效控制,但影响疫情暴发的主要原因仍然是边远农村的农民,及学校饮用水被污染所造成。%Guangxi is the more serious epidemic of typhoid and paratyphoid one of the provinces in China and had typhoid fever and paratyphoid fever cases occur throughout the year. The typhoid epidemic main and cases of typhoid fever occur annually a peak of epidemic from July to October in Guangxi before 1996. The epidemic paratyphoid have been found since the 1996, the monitoring found that there are two peak of the epidemic to the 1999 and namely in May of paratyphoid fever and in October of typhoid each one peak. But nearly 10 years of monitoring found two peak times were very close of the time respectively in July and August from 2004 to 2010.The population incidence of typhoid fever was 3.96/100 thousand, 8.83/100 thousand, 3.55/100 thousand 5.04/100 thousand 5.04/100 thousand and 9.74/100 thousand in Guangxi from the 1950's to the 1990's. The average annual incidence rate 10.27/100 thousand in Guangxi from 1993 to 2002. The typhoid incidence rate fluctuations between the 1.61/100 thousand and 5.41/100 thousand , the

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

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    McArthur, Monica A; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2015-05-01

    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.

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

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    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.

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

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    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.

  9. 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.

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

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    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.

  11. 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.

  12. Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.

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    Brown, Eric M; Wlodarska, Marta; Willing, Benjamin P; Vonaesch, Pascale; Han, Jun; Reynolds, Lisa A; Arrieta, Marie-Claire; Uhrig, Marco; Scholz, Roland; Partida, Oswaldo; Borchers, Christoph H; Sansonetti, Philippe J; Finlay, B Brett

    2015-08-04

    Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli, remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease.

  13. Chronic cholecystitis

    Science.gov (United States)

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  14. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  15. Chronic Pain

    Science.gov (United States)

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis ...

  16. Combined rapid (TUBEX test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity.

    Directory of Open Access Journals (Sweden)

    Meiying Yan

    Full Text Available Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12 found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively. Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0% or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6, respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA--such specimens might have been storage-denatured (especially the older paratyphoid samples or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera

  17. Chronic prostatitis

    OpenAIRE

    Le, Brian; Schaeffer, Anthony J.

    2011-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  18. Chronic prostatitis

    OpenAIRE

    Erickson, Bradley A.; Schaeffer, Anthony J.; Le, Brian

    2008-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  19. Cloning and expression of murine immune interferon cDNA.

    OpenAIRE

    1983-01-01

    The murine immune interferon (IFN-gamma) gene was cloned and expressed under control of the simian virus 40 early promoter in the monkey COS-1 cell line. A protein is secreted from these cells having the biological, antigenic, and biochemical characteristics of natural murine IFN-gamma. Cloned murine IFN-gamma cDNAs were obtained by using RNA from both mitogen-induced murine spleens and the transfected COS cells, and both code for identical proteins. The mature murine IFN-gamma encoded is 136...

  20. 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

  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. An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein

    OpenAIRE

    Ahmadi, Abbas; Nikkhoo, Bahram; Mokarizadeh, Aram; Rahmani, Mohammad-Reza; Fakhari, Shohreh; Mohammadi, Mehdi; Jalili, Ali

    2016-01-01

    Introduction Chronic pancreatitis (CP) is an intractable and multi-factorial disorder. Developing appropriate animal models is an essential step in pancreatitis research, and the best ones are those which mimic the human disorder both aetiologically and pathophysiologically. The current study presents an optimised protocol for creating a murine model of CP, which mimics the initial steps of chronic pancreatitis in alcohol chronic pancreatitis and compares it with two other mouse models treate...

  3. Development of renal atrophy in murine 2 kidney 1 clip hypertension is strain independent.

    Science.gov (United States)

    Kashyap, Sonu; Boyilla, Rajendra; Zaia, Paula J; Ghossan, Roba; Nath, Karl A; Textor, Stephen C; Lerman, Lilach O; Grande, Joseph P

    2016-08-01

    The murine 2-kidney 1-clip (2K1C) model has been used to identify mechanisms underlying chronic renal disease in human renovascular hypertension. Although this model recapitulates many of the features of human renovascular disease, strain specific variability in renal outcomes and animal-to-animal variation in the degree of arterial stenosis are well recognized limitations. In particular, the C57BL/6J strain is considered to be resistant to chronic renal damage in other models. Our objectives were to determine strain dependent variations in renal disease progression and to identify parameters that predict renal atrophy in murine 2K1C hypertension. We used a 0.20mm polytetrafluoroethylene cuff to establish RAS in 3 strains of mice C57BL/6J (N=321), C57BLKS/J (N=177) and129Sv (N=156). The kidneys and hearts were harvested for histopathologic analysis after 3days or after 1, 2, 4, 6, 7, 11 or 17weeks. We performed multivariate analysis to define associations between blood pressure, heart and kidney weights, ratio of stenotic kidney/contralateral kidney (STK/CLK) weight, percent atrophy (% atrophy) and plasma renin content. The STK of all 3 strains showed minimal histopathologic alterations after 3days, but later developed progressive interstitial fibrosis, tubular atrophy, and inflammation. The STK weight negatively correlated with maximum blood pressure and % atrophy, and positively correlated with STK/CLK ratio. RAS produces severe chronic renal injury in the STK of all murine strains studied, including C57BL/6J. Systolic blood pressure is negatively associated with STK weight, STK/CLK ratio and positively with atrophy and may be used to assess adequacy of vascular stenosis in this model.

  4. 小儿伤寒的外科并发症%Surgical Complications of Typhoid Fever in Children

    Institute of Scientific and Technical Information of China (English)

    董蒨; 金百祥

    1990-01-01

    Thirteen caese with surgical complication of typhoid fever,intestinal perforation(9),acute cholecystitis(2),splenic abcess(1)and massive intestinal bleeding(1)were treated from 1960 to 1988.These complications presented from 4 to 28 days since running fever.Widal's test was positive in 10 cases.The diagnosis was also established by tb e positive culture of salmonella typh in tbe stool(6),blood(4),and bile juice or pus(8).All cases were operated on,and 3 diedpostoperatively.%本文报道小儿伤寒的外科并发症13例.肠穿孔9例,胆囊炎2例,脾脓肿及肠道大出血各1例.临床表现、wi dal试验、大便、血、脓液或胆汁培养是主要诊断依据.均手术治疗,死亡3例.强调全面实验室检查及早期手术.

  5. Serological follow-up after non-typhoid salmonella infection in humans using a mixed lipopolysaccharide ELISA.

    Science.gov (United States)

    Falkenhorst, Gerhard; Ceper, Tina H; Strid, Mette A; Mølbak, Kåre; Krogfelt, Karen A

    2013-12-01

    In industrialized countries, non-typhoid salmonella are a frequent cause of bacterial gastroenteritis. Diagnosis is usually made by stool culture, which is labour-intensive and time-consuming. Sensitivity depends on handling of stool samples and delay from illness onset to sampling. We developed an indirect mixed enzyme-linked immunosorbent assay (ELISA) for the detection of human serum antibodies against lipopolysaccharide antigens of the two predominant serovars, Salmonella serovar Enteritidis (S. Enteritidis) and S. Typhimurium. We measured IgA, IgM and IgG in 964 sera from 302 patients with stool culture-confirmed acute salmonella gastroenteritis, in 300 sera from healthy blood donors, and in 147 sera from patients with antibodies against other bacteria. Patient sera were collected within 1 month and approximately 3, 6, and 12 months after illness onset. For sera collected ≤ 30 days of onset, sensitivity of the ELISA was 92% for S. Enteritidis and 86% for S. Typhimurium, with a specificity of 95% for both serovars. The mixed ELISA is a useful additional tool for the diagnosis of acute salmonella gastroenteritis. It allows rapid analysis of multiple samples, thus can be used for sero-epidemiological studies of large population-based serum collections in order to estimate the population incidence of salmonella infections. Another application is aetiological diagnostics in patients with suspected post-infectious complications such as reactive arthritis, even when faecal shedding of salmonella has ceased.

  6. Prevalence of quinolone resistance determinants in non-typhoidal Salmonella isolates from human origin in Extremadura, Spain.

    Science.gov (United States)

    Campos, Maria Jorge; Palomo, Gonzalo; Hormeño, Lorena; Herrera-León, Silvia; Domínguez, Lucas; Vadillo, Santiago; Píriz, Segundo; Quesada, Alberto

    2014-05-01

    Resistance to the quinolones nalidixic acid (NAL) and ciprofloxacin (CIP) and the occurrence of quinolone resistance determinants have been investigated in 300 non-typhoidal Salmonella from human origin, isolated in the years between 2004 and 2008, in 6 hospitals within Extremadura (Spain). Salmonella Enteritidis was the major serotype found among quinolone-resistant isolates, most of which were clustered by clonal analysis to a single clone, which presented D87 or S83 substitutions in GyrA. Eleven isolates presented the non-classical quinolone resistance phenotype (resistance to CIP and susceptibility to NAL), lacking mutations in the quinolone resistance determinant region of topoisomerase genes. Among them, one Salmonella Typhimurium isolate carried a qnrS1 gene in a low-molecular-weight plasmid, pQnrS1-HLR25, identical to plasmids previously found in the UK, Taiwan, and USA. The occurrence of this genetic element could represent a risk for the horizontal transmission of quinolone resistance among Enterobacteriaceae in the Iberian Peninsula.

  7. 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.

  8. 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.

  9. 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

  10. A role of NF-E2 in chronic inflammation and clonal evolution in essential thrombocythemia, polycythemia vera and myelofibrosis?

    Science.gov (United States)

    Hasselbalch, Hans C

    2014-02-01

    A novel murine model for myeloproliferative neoplasms (MPNs) generated by overexpression of the transcription factor NF-E2 has recently been described. Sustained overexpression of NF-E2 in this model induced myeloid expansion with anemia, leukocytosis and thrombocytosis. Herein, it is debated if NF-E2 overexpression also might have induced a sustained state of in vivo leukocyte and platelet activation with chronic and self-perpetuating production of inflammatory products from activated leukocytes and platelets. If so, this novel murine model also may excellently describe the deleterious impact of sustained chronic NF-E2 overexpression during uncontrolled chronic inflammation upon the hematopoietic system--the development of clonal myeloproliferation. Accordingly, this novel murine model may also have delivered the proof of concept of chronic inflammation as a trigger and driver of clonal evolution in MPNs.

  11. Murine Typhus: Clinical and epidemiological aspects

    Directory of Open Access Journals (Sweden)

    Gaspar Peniche Lara

    2012-06-01

    Full Text Available 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.

  12. 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.

  13. 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.

  14. Immune dynamics following infection of avian macrophages and epithelial cells with typhoidal and non-typhoidal Salmonella enterica serovars; bacterial invasion and persistence, nitric oxide and oxygen production, differential host gene expression, NF-κB signalling and cell cytotoxicity.

    Science.gov (United States)

    Setta, Ahmed; Barrow, Paul A; Kaiser, Pete; Jones, Michael A

    2012-05-15

    Poultry-derived food is a common source of infection of human with the non-host-adapted salmonellae while fowl typhoid and pullorum disease are serious diseases in poultry. Development of novel immune-based control strategies against Salmonella infection necessitates a better understanding of the host-pathogen interactions at the cellular level. Intestinal epithelial cells are the first line of defence against enteric infections and the role of macrophages is crucial in Salmonella infection and pathogenesis. While gene expression following Salmonella infection has been investigated, a comparison between different serovars has not been, as yet, extensively studied in poultry. In this study, chicken macrophage-like cells (HD11) and chick kidney epithelial cells (CKC) were used to study and compare the immune responses and mechanisms that develop after infection with different Salmonella serotypes. Salmonella serovars Typhimurium, Enteritidis, Hadar and Infantis showed a greater level of invasion and/or uptake characters when compared with S. Pullorum or S. Gallinarum. Nitrate and reactive oxygen species were greater in Salmonella-infected HD11 cells with the expression of iNOS and nuclear factor-κB by chicken macrophages infected with both systemic and broad host range serovars. HD11 cells revealed higher mRNA gene expression for CXCLi2, IL-6 and iNOS genes in response to S. Enteritidis infection when compared to S. Pullorum-infected cells. S. Typhimurium- and S. Hadar-infected HD11 showed higher gene expression for CXCLi2 versus S. Pullorum-infected cells. Higher mRNA gene expression levels of pro-inflammatory cytokine IL-6, chemokines CXCLi1 and CXCLi2 and iNOS genes were detected in S. Typhimurium- and S. Enteritidis-infected CKC followed by S. Hadar and S. Infantis while no significant changes were observed in S. Pullorum or S. Gallinarum-infected CKC.

  15. 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.

  16. [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.

  17. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  18. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  19. 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.

  20. 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。

  1. Exploring the translational disconnect between the murine and human inflammatory response: analysis of LPS dose–response relationship in murine versus human cell lines and implications for translation into murine models of sepsis

    Directory of Open Access Journals (Sweden)

    McCarron EP

    2015-10-01

    Full Text Available Eamon P McCarron,1 Dominic P Williams,1 Daniel J Antoine,1 Anja Kipar,2 Jana Lemm,3 Sebastian Stehr,3 Ingeborg D Welters,4 1Department of Clinical and Molecular Pharmacology, Centre for Drug Safety Science, Institute of Translational Medicine, 2Department of Veterinary Pathology, University of Liverpool, Liverpool, UK; 3Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; 4Department of Obesity and Endocrinology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Background: Inflammation forms an important part of the human innate immune system and is largely dependent on the activation of the "classical" NF-κB pathway through Toll-like receptors (TLRs. Understanding this has allowed researchers to explore roles of therapeutic targets in managing conditions such as sepsis. Recapitulating an inflammatory response using lipopolysaccharide (LPS, a "sterile" technique, can provide information that is dissimilar to the clinical condition. By examining NF-κB activation (through immunoblotting of the p65 subunit in two separate cell lines (murine and human and analyzing two murine models of sepsis (intraperitoneal [IP] LPS and IP stool inoculation, an evaluation of the translational disconnect between experimental and clinical sepsis can be made. Methods: THP-1 (human cells and RAW 264.7 (murine cells were dosed with concentrations of LPS (human, 1 pg/mL to 100 ng/mL; murine, 30 pg/mL to 1,000 ng/mL and nuclear actin and p65 were immunoblotted to measure changes in nuclear density. In vivo, C57BL/6 mice received either IP injection of stool suspension (5 µL/g or LPS (25 mg/kg or saline (1 mL/kg. Animals were culled at 6 hours and tissues were analyzed. Results: An increase in basal p65:actin density in THP-1 cells (mean 0.214, standard error of the mean 0.024 was seen at doses as small as 0.1 ng/mL (0.519±0.064. In contrast to RAW 264.7 cells, basal increases (0.170±0

  2. Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach

    Science.gov (United States)

    Kimura, Yuto; Ikuta, Kozo; Kimura, Takeshi; Chiba, Tsutomu; Oshima, Hiroko; Oshima, Masanobu; Nishi, Eiichiro; Seno, Hiroshi

    2017-01-01

    Chronic inflammation contributes to a wide variety of human disorders. In the stomach, longstanding gastritis often results in structural alterations in the gastric mucosa, including metaplastic changes and gastric cancers. Therefore, it is important to elucidate factors that are involved in gastric inflammation. Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins. Here, we have demonstrated that Nrdc crucially regulates gastric inflammation caused by Helicobacter felis infection or forced expression of prostaglandin E2 in K19-C2mE mice. Metaplastic changes following gastric inflammation were suppressed by the deletion of Nrdc. Furthremore, the deletion of Nrdc significantly suppressed N-methyl-N-nitrosourea (MNU)-induced gastric tumorigenesis in the murine stomach. These data may lead to a global therapeutic approach against various gastric disorders by targeting Nrdc. PMID:28230087

  3. Hamster and Murine Models of Severe Destructive Lyme Arthritis

    Directory of Open Access Journals (Sweden)

    Erik Munson

    2012-01-01

    Full Text Available Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ- deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology.

  4. 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.

  5. Toxigenicity testing of clinical isolates of non-typhoidal salmonellae in Vero cell culture & Caenorhabditis elegans model.

    Science.gov (United States)

    Jesudason, Mary V; V Balaji, V; Densibai, Shoba

    2006-06-01

    The non-typhoidal salmonellae (NTS) are recognized agents of gastroenteritis worldwide. Some of the NTS do not produces cytotoxic changes in tissue culture and not much is known about the endotoxicity of the clinical isolates of NTS (mostly Salmonella enterica serotype Typhimurium and Salmonella enterica serotype Enteritidis). We examined the exotoxic (cytotoxin) and endotoxic activity of clinical isolates of NTS in two assay models namely Vero cell culture and the nematode, Caenorhabditis elegans. Bacteria-free culture supernatants of 40 isolates NTS were tested in 96 well microtitre plate containing confluent monolayers of Vero cells. For the effects on C. elegans, the worms were exposed to bacteria free culture supernatants in 24 well microtitre plate for 24 h and then transferred to OP50 Escherichia coli lawn culture. The endotoxic activity of the live bacterium was studied by feeding the worms in the lawn culture of NTS separately. No cytopathic effect was observed with NTS tested in Vero cell culture assay. Likewise, the worms exposed to the bacteria-free culture supernatants were found active up to 7 days. In the co-culture killing assay, worms were found dead with characteristic stiff and straight appearance by 16(th) day. The worms were alive up to 21 days in OP50 E. coli. Bacteria-free culture supernatants did not have any deleterious effect on worms or in Vero cell culture, suggesting that there is no soluble toxic factor (diffusible toxin) in the culture supernatants. However, live NTS were found to be lethal to the worms; indicating that direct interaction between viable NTS and C. elegans is necessary for killing.

  6. 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

    2015-12-02

    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.

  7. 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, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

  8. 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.

  9. [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.

  10. Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays

    Directory of Open Access Journals (Sweden)

    Yuan Xin Goay

    2016-01-01

    Full Text Available Salmonella Typhi (S. Typhi causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S. Typhi with other enteric pathogens was performed, and 6 S. Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico. Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro. The diagnostic sensitivities and specificities of each assay were determined using 39 S. Typhi, 62 non-Typhi Salmonella, and 10 non-Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39 and 100% specificity (0/72. The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

  11. 小儿非典型伤寒50例临床观察%Clinical Observation of 50 Cases of Children with Atypical Typhoid

    Institute of Scientific and Technical Information of China (English)

    沈海燕

    2013-01-01

    目的:分析小儿非典型伤寒的临床治疗体会。方法选取我院近几年收治的非典型伤寒50例患儿资料进行回顾性分析。结果全部病例确认后经用先锋必,头孢曲松钠,及对症治疗10~14d,全部治愈。结论加强对此病的认识,及时作出正确诊断,减少小儿非典型伤寒的漏误诊,及时合理选用有效的抗生素治疗,对减少并发症的发生和控制并发症有重要意义。%Objective: to analyze the clinicallexperience in treatment of children with atypicallof typhoid fever. Methods: in our hospitallin recent years were atypicallof typhoid fever in 50 cases were retrospectively analyzed. Results: allcases were confirmed by cefoperazone sodium, ceftriaxone sodium, and symptomatic treatment of 10~14d, allcured. Conclusion:strengthen the understanding of this disease, to make the right diagnosis, reduce misdiagnosis of atypicalltyphoid, timely and reasonable use of antibiotics and Effective, is of great significance to reduce the incidence of complications and controllcomplications.

  12. Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever.

    Science.gov (United States)

    Ortiz, V; Isibasi, A; García-Ortigoza, E; Kumate, J

    1989-07-01

    The studies reported here were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce a humoral immune response in humans with typhoid fever. OMPs were isolated with the nonionic detergent Triton X-100 and were found to be contaminated with approximately 4% lipopolysaccharide. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns showed protein bands with molecular size ranges from 17 to 70 kilodaltons; the major groups of proteins were those that correspond to the porins and OmpA of gram-negative bacteria. Rabbit antiserum to OMPs or to S. typhi recognized OMPs after absorption with lipopolysaccharide. Sera from patients with typhoid fever contained immunoglobulin M antibodies which reacted with a protein of 28 kilodaltons and immunoglobulin G antibodies which reacted mainly with the porins, as determined by immunoblotting. These results indicate that the porins are the major immunogenic OMPs from S. typhi and that the immune response induced in the infection could be related to the protective status.

  13. Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays.

    Science.gov (United States)

    Goay, Yuan Xin; Chin, Kai Ling; Tan, Clarissa Ling Ling; Yeoh, Chiann Ying; Ja'afar, Ja'afar Nuhu; Zaidah, Abdul Rahman; Chinni, Suresh Venkata; Phua, Kia Kien

    2016-01-01

    Salmonella Typhi (S. Typhi) causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S. Typhi with other enteric pathogens was performed, and 6 S. Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico. Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro. The diagnostic sensitivities and specificities of each assay were determined using 39 S. Typhi, 62 non-Typhi Salmonella, and 10 non-Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39) and 100% specificity (0/72). The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

  14. Ear infection - chronic

    Science.gov (United States)

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... up. When this happens, infection can occur. A chronic ear infection develops when fluid or an infection ...

  15. 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

  16. 伤寒疟疾重叠感染12例临床分析%Clinical Analysis on 12 Cases of Double Infected with Typhoid Fever and Malaria

    Institute of Scientific and Technical Information of China (English)

    王勇; 张承红; 彭勇

    2000-01-01

    Objective: To study the clinical manifestation, diagnosis and treatment status of double infected with typhoid fever and malaria in Jinghong. Method: To analyze 12 cases (male 10 and female 2) of double infected with typhoid fever and malaria over the past ten years in our hospital. Results: Of them, 8 cases suffered fioom typhoid fever with tertian malaria, 3 cases of typhoid fever with falciparum nalaria, anid the other one was diagnosed by anti-malaria treatment. Conclusion: We should consider the possibility of typhoid fever accompanied malaria in the epidemic area and season of malaria.%目的:分析景洪地区伤寒、疟疾重叠感染的临床表现及诊治情况。方法:收集我院近十年来的伤寒、疟疾重叠感染患者12例(其中男10例,女2例)结果:12例伤寒重叠感染间日疟8例、恶性疟3例,疟原虫阴性的1例是在确诊伤寒后,按伤寒治疗,高热持续不退,贫血加重,经诊断性抗疟治疗,体温降至正常才诊断为重叠感染的。结论:在疟疾流行地区、流行季节,诊断伤寒时,要考虑重叠感染疟疾的可能。

  17. 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

  18. [Chronic hepatitis].

    Science.gov (United States)

    Figueroa Barrios, R

    1995-01-01

    Medical literature about chronic hepatitis is reviewed. This unresolving disease caused by viruses, drugs or unknown factors may progress to in cirrhosis and hepatocarcinoma. A classification based on liver biopsy histology into chronic persistent and chronic active types has been largely abandoned and emphasis is placed on recognizing the etiology of the various types. One is associated with continuing hepatitis B virus infection; another is related to chronic hepatitis C virus infection and the third is termed autoinmune, because of the association with positive serum autoantibodies. A fourth type with similar clinical functional and morphologic features is found with some drug reactions. Long term corticoesteroid therapy is usually successful in autoinmune type. Associations between antibodies to liver-kidney microsomes and the hepatitis C virus can cause diagnostic difficulties. Antiviral treatment of chronic hepatitis B and C with interpheron alfa is employed, controlling symptoms and abnormal biochemistry and the progression to cirrhosis and liver cancer in 30 to 40% patients. Alternative therapies or combinations with interpheron are being evaluated waiting for final results.

  19. Posttraumatic Chondrocyte Apoptosis in the Murine Xiphoid

    Science.gov (United States)

    Davis, Christopher G.; Eisner, Eric; McGlynn, Margaret; Shelton, John M.; Richardson, James

    2013-01-01

    Objective. To demonstrate posttraumatic chondrocyte apoptosis in the murine xiphoid after a crush-type injury and to ultimately determine the pathway (i.e., intrinsic or extrinsic) by which chondrocytes undergo apoptosis in response to mechanical injury. Design. The xiphoids of adult female wild-type mice were injured with the use of a modified Kelly clamp. Postinjury xiphoid cartilage was analyzed via 3 well-described independent means of assessing apoptosis in chondrocytes: hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and activated caspase-3 staining. Results. Injured specimens contained many chondrocytes with evidence of apoptosis, which is characterized by cell shrinkage, chromatin condensation, nuclear fragmentation, and the liberation of apoptotic bodies. There was a statistically significant increase in the number of chondrocytes undergoing apoptosis in the injured specimens as compared with the uninjured specimens. Conclusions. Chondrocytes can be stimulated to undergo apoptosis as a result of mechanical injury. These experiments involving predominantly cartilaginous murine xiphoid in vivo establish a baseline for future investigations that employ the genetic and therapeutic modulation of chondrocyte apoptosis in response to mechanical injury. PMID:26069679

  20. Thermal resistance in a spontaneous murine tumour.

    Science.gov (United States)

    Maher, J; Urano, M; Rice, L; Suit, H D

    1981-12-01

    Resistance to subsequent hyperthermia as a result of prior heating was investigated using a spontaneous murine tumour implanted into the feet of C3H/Sed mice. Tumours were treated by immersing the tumour-bearing foot into a constant-temperature hot water bath set at 45.5 degrees C and were given single and split doses of heat. Response was assessed using a tumour-growth time assay. Three aspects of thermally-induced resistance were particularly considered: the time course of development and decay; the importance of the magnitude of the priming dose and the influence of the size of the tumour at the time of treatment. Substantial resistance was induced in this tumour by short priming doses at 45.5 degrees C, rising rapidly 1-2 days after the first treatment and then starting to decay. There was no significant difference in the kinetics of thermal resistance induced in tumours treated at 4mm and those treated at 8 mm in size, although the large tumours were more sensitive to single doses of heat. Increasing the magnitude of the priming dose of heat resulted in an increase in the magnitude of resistance to the second dose. The results of this study are compared with results of similar studies in this and other laboratories using murine normal tissues and cells in culture. Possible clinical implications are considered.

  1. 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.

  2. 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.

  3. 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.

  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. 小儿伤寒60例误诊分析%Analysis of causes in misdiagnosis of 60 infant typhoid fever cases

    Institute of Scientific and Technical Information of China (English)

    何山

    2011-01-01

    Objectives To analyze causes of misdiagnosis infant cases with typhoid fever. Methods The causes of 60 misdiagnosed infant cases out of the 93 hospitalized typhoid fever cases Lingao County Traditional Chinese Medicine Hospital from January 1995 to June 2010 were analyzed. Results Of the 93 infant typhoid fever cases 60 were initially misdiagnosed as other illness with a misdiagnosis rate of 64.5% ,including 29 cases were misdiagnosed as upper respiratory tract infection,others were misdiagnosed as pneumonia,bronchitis,bacterial dysentery,septicemia,viral myocarditis,viral hepatitis,anemia of unknown origin,tuberculosis,infectious mononucleosis, Kawasaki disease. Conclusion To reduce the misdiagnostic rate, detailed medical history record, physical examination, observation of manifestations and signs,conventional eosinophil count, Widal reaction, blood cultures,stool culture and other laboratory tests be carried out.%目的 探讨小儿伤寒误诊的原因,减少误诊率.方法收集1995年1月~2010年月6月收治住院确诊的93例小儿伤寒病例中,初诊误为其他病种的患儿60例进行分析.结果 93例小儿伤寒中误诊为非伤寒者60例,误诊率为64.5%,以误诊上呼吸道感染最多(29例),肺炎(9例),支气管炎、菌痢、败血症(4~5例),病毒性心肌炎、病毒性肝炎、贫血原因待查、肺结核、传染性单核细胞增多症和川崎病(1~2例).结论 详细收集病史,仔细体检,动态观察体征的变化,常规计数嗜酸性粒细胞和肥达反应,及时做血培养及粪培养等实验室检查是减少误诊、漏诊的关键.

  6. Moxifloxacin for 78 Cases of Typhoid%莫西沙星治疗78例伤寒的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    潘云虎; 季志宇; 陈艺坛; 陈光; 熊勇

    2011-01-01

    Objective: To evaluate the efficiency and safety of moxif loxacin on typhoid patients. Methods: 78 typhoid patients were randomly divided into trial group and control group, The 39 trial group members were treated with moxifloxacin, In the control group, 39 patients were treated with levofloxacin, intravenous dripping every day until normal temperature for 7d. Results: After treatment, the cured rate in the trial group was 94.8%, while for the control group was 92.3%(P > 0.05). The time of reducing fever and returning to normal temperature is shorter in the trial group than in the control group, it was significant differences in two group(P<0.05), and the treatment of reaction was significant lower in the trial group than in the control group (P<0.05). Conclusion: Moxifloxacin is effective and safe in the treatment of typhoid patients, and has good prospects in clinical application.%目的:探讨莫西沙星在伤寒治疗中的临床意义.方法:将我院2008年6月至2010年6月期间78例确诊的伤寒患者随机分为治疗组(39例)和对照组(39例),治疗组给予莫西沙星,对照组给予盐酸左氧氟沙星,均静脉滴注,每日1次,体温正常后7d停药.结果:治疗组痊愈率94.8%,总有效率100%;对照组痊愈率92.3%,总有效率100%,两组痊愈率差异无统计学意义(P<0.05);治疗组开始退热和体温降至正常的时间均较对照组缩短,差异有显著意义(P<0.05).治疗组不良反应发生率明显低于对照组(P<0.05).结论:莫西沙星在伤寒治疗中具有疗效确切、无复发、副作用少等特点,在治疗非耐药和耐药伤寒中有重要作用,有较好的临床应用前景.

  7. Skeletal muscle mitochondrial uncoupling in a murine cancer cachexia model.

    Science.gov (United States)

    Tzika, A Aria; Fontes-Oliveira, Cibely Cristine; Shestov, Alexander A; Constantinou, Caterina; Psychogios, Nikolaos; Righi, Valeria; Mintzopoulos, Dionyssios; Busquets, Silvia; Lopez-Soriano, Francisco J; Milot, Sylvain; Lepine, Francois; Mindrinos, Michael N; Rahme, Laurence G; Argiles, Josep M

    2013-09-01

    Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We subjected mice to in vivo phosphorous-31 nuclear magnetic resonance (31P NMR) spectroscopy and subjected murine skeletal muscle samples to gas chromatography/mass spectrometry (GC/MS). The mice used in both experiments were Lewis lung carcinoma models of cancer cachexia. A novel 'fragmented mass isotopomer' approach was used in our dynamic analysis of 13C mass isotopomer data. Our 31P NMR and GC/MS results indicated that the adenosine triphosphate (ATP) synthesis rate and tricarboxylic acid (TCA) cycle flux were reduced by 49% and 22%, respectively, in the cancer-bearing mice (p<0.008; t-test vs. controls). The ratio of ATP synthesis rate to the TCA cycle flux (an index of mitochondrial coupling) was reduced by 32% in the cancer-bearing mice (p=0.036; t-test vs. controls). Genomic analysis revealed aberrant expression levels for key regulatory genes and transmission electron microscopy (TEM) revealed ultrastructural abnormalities in the muscle fiber, consistent with the presence of abnormal, giant mitochondria. Taken together, these data suggest that mitochondrial uncoupling occurs in cancer cachexia and thus point to the mitochondria as a potential pharmaceutical target for the treatment of cachexia. These findings may prove relevant to elucidating the mechanisms underlying skeletal muscle wasting observed in other chronic diseases, as well as in aging.

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

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    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.

  9. Helicobacter pylori impairs murine dendritic cell responses to infection.

    Directory of Open Access Journals (Sweden)

    Ya-Hui Wang

    Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

  10. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J.; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C. A.

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into l

  11. 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

  12. Chronic gastritis.

    Science.gov (United States)

    Sipponen, Pentti; Maaroos, Heidi-Ingrid

    2015-06-01

    Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.

  13. Chronic Bronchitis

    Science.gov (United States)

    ... breathing. You may also have other tests. Chronic bronchitis is a long-term condition that keeps coming back or never goes away completely. If you smoke, it is important to quit. Treatment can help with your symptoms. It often includes ...

  14. 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.

  15. 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.

  16. 肠伤寒穿孔手术治疗预后的影响因素分析%Factors Influencing Prognosis of Surgical Treatment in Typhoid Perforation

    Institute of Scientific and Technical Information of China (English)

    杨洪范

    2012-01-01

    Objective To study the factors affecting prognosis in patients with typhoid ileal perforation and to offer strategies for improvement. Methods The clinical records of 295 patients who underwent surgery because of typhoid enteric perforation in the Department of Surgery, Regional Hospital of Maradi, Niger, from January 2010 to December 2011 , were reviewed retrospectively. Seven of potential prognostic factors were examined by the x2 test and the multiple Logistic regression analysis. Results The mortality rate was 20.7% ( 61/295 ). Lnivariate analysis revealed that age, number of perforation, perforation-operation interval( PO1 ) and postoperative faecal fistula were significantly associated with prognosis of typhoid ileal perforation( P < 0. 05 ). Multiple Logistic regression analysis showed that perforation-operation interval( OR -4. 723 ,95% CI -1.403 - 15. 897,P< 0.05 )and postoperative faecal fistula( OR -3. 334 ,95% CI = 1. 102-10. 087 , P < 0. 05 )were closely associated with the prognosis. Conclusion Perforation-ope ration interval and postoperative faecal fistula are significant independent factors influencing prognosis of surgical treatment in typhoid perforation. Early diagnosis and timely surgical intervention could improve the prognosis.%目的 探讨影响肠伤寒穿孔手术治疗预后的因素,为改善预后提供帮助.方法 回顾性分析2010年1月至2011年12月中国援尼日尔医疗队工作点玛拉迪地方医院外科295例肠伤寒穿孔患者的临床资料.应用χ2检验和多因素Logistic回归分析影响预后的因素.结果 295例均手术治疗,病死率为20.7%(61/295).单因素分析结果显示年龄、穿孔-手术间隔、穿孔数量和术后肠瘘与肠伤寒穿孔手术治疗的预后相关(P<0.05).多因素Logistic 回归分析显示:穿孔-手术间隔(OR=4.723,95% CI=1.403 ~15.897,P<0.05)、术后肠瘘(OR=3.334,95% CI=1.102 ~10.087,P<0.05)与肠伤寒穿孔手术治疗的预后密切相关.结论 穿孔-手

  17. Human-oriented Thought of Questions on Typhoid Theory(Shanghan Zhiyi)%《伤寒质难》以人为本思想浅探

    Institute of Scientific and Technical Information of China (English)

    吕崇江; 李学麟

    2009-01-01

    是民国时期沪上著名中医学家祝味菊先生学术思想的代表作,该书立足于人体本身,治人为主,倡导本体疗法及自然疗能,治病疗疚时以人为本,因而疗效卓越.%Questions on Typhoid Theory is a representative academic book of ZHU Wei-ju,a well-known TCM doctor of Shanghai in the period of the republic of China.The thoughts of the book is based on human body itself,advocating focusing on body itself not diseases,self recovery and natural therapy.Because he put human in the first place,he got excellent therapeutic effects in clinic.

  18. 徐荣斋对绍派伤寒的贡献%Mr.Xu Rongzhai's Contribution to Shao School Typhoid Fever

    Institute of Scientific and Technical Information of China (English)

    沈钦荣

    2011-01-01

    Mr. Xu Rongzhai,contemporary TCM classical master, with fashion of exploring the origin of Shao School typhoid fever and starting Shao School study.wrote "Revise Common Treatise on Febrile Disease",first was to make a summary,and second was elucidation,supplement and correction, extruding practical applicability, without regulating structure; while the revision was all made from practice.%徐荣斋先生,当代中医经学名家,其学探绍派伤寒之源流、启绍派研究之风气。著《重订通俗伤寒论》,一作提要,二作阐发、补充、辨误,突出实用性,不调整结构,而增删内容,都从临证实用出发。

  19. Diaphorase Measurement for Infantile Typhoid Fever Infection and Its Clinical Signiflcance%伤寒患儿血清心肌酶测定及临床意义

    Institute of Scientific and Technical Information of China (English)

    张哲梅; 杨卫民; 肖庆生; 叶小净

    2006-01-01

    目的探讨伤寒患儿(typhoid fever)心肌酶变化的临床意义.方法用全自动分析仪检测磷酸肌酸激酶(CK)及磷酸肌酸激酶同功酶(CK-MB),乳酸脱氢酶(LDH),天冬氨酸转氨酶(AST).结果伤寒组CK、CK-MB、LDH、AST异常高于健康组,差异非常显著;伤寒组心肌酶值(u/l)明显高于健康组,其中CK,CK-MB、LDH、AST有显著或非常显著差异.结论小儿伤寒可明显地影响心肌酶学改变,但检测值的增高并不一定都提示心肌损伤存在.

  20. Febre tifóide: recaída por resistência antimicrobiana. Relato de caso Typhoid fever: relapse due to antimicrobial resistance. Case report

    Directory of Open Access Journals (Sweden)

    Wilson Duarte Alecrim

    2002-12-01

    Full Text Available Relatamos pela primeira vez na Amazônia Brasileira um paciente com febre tifóide, com resistência clínica e laboratorial ao cloranfenicol, droga de escolha para esta doença em nossa região. A recaída foi observada no 7° dia após o término do tratamento e a paciente foi tratada com ciprofloxacina.We report for the first time in the Brazilian Amazon a typhoid fever patient with clinical and laboratorial resistance to chloramphenicol, drug of election for this disease in our region. The relapse was observed at the 7th day after the end of treatment and the patient was treated with ciprofloxacin.

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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.

  3. 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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. 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.

  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. 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

    2016-06-01

    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.

  10. 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.

  11. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... Information > Children/Pediatric > Chronic Pancreatitis in Children test Chronic Pancreatitis in Children What symptoms would my child ... pancreatitis will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are ...

  12. Chronic Beryllium Disease

    Science.gov (United States)

    ... Science Education & Training Home Conditions Chronic Beryllium Disease Chronic Beryllium Disease Make an Appointment Find a Doctor ... MD, MSPH, FCCP (February 01, 2016) What is chronic beryllium disease (CBD)? Chronic beryllium disease (CBD) is ...

  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)

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

  15. Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Jalilian, Babak; Keller, Kresten Krarup;

    2016-01-01

    in murine models of rheumatoid arthritis. METHODS: The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice...... associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above...

  16. Surveillance of typhoid and paratyphoid in China, 2009%2009年全国伤寒和副伤寒监测分析

    Institute of Scientific and Technical Information of China (English)

    常昭瑞; 张伟东; 闫梅英; 王子军; 张静; 孙军玲

    2011-01-01

    Objective To understand the incidence trend of typhoid and paratyphoid, the major pathogen in area with high incidence and the bacteria carriage in risk population as well as the bacteria drug resistance in China.Methods Descriptive epidemioiogical analysis was conducted on the incidence data of typhoid and paratyphoid by network direct reporting and thc surveillance results in national surveillance sites in China in 2009. Results Totally 16 938 cases of typhoid and paratyphoid were reported, including 9 deaths, of which 12 427 were typhoid cases ( including 7 deaths); 4511 were paratyphoid cases (including 2 deaths); Compared with 2008, the typhoid cases increased by 13.53% and paratyphoid cases declined by 3.92%. Yunnan, Guizhou, Guangdong, Guangxi, Zhejiang and Hunan remained to be the provinces with high incidences of the disease. The detection of patients' specimen indicated that the positive rate in clinically diagnosed cases ( 19. 23% ) was higher than that in suspected cases (4. 56% ). The predominant pathogen isolated was Salmonella paratyphi A, accounting for 60.69% of the total isolates. The drug resistance rate of Salmonella typhi was higher than that of Salmonella paratyphi. The drug resistance spectrum varied by regions. The PFEG indicated that JKPX01. CN0001 were the prevalent patterns of paratyphoid A in area with high incidence. Conclusion The overall incidence of typhoid and paratyphoid declined in China, but the situation in some provinces was still serious. It is necessary to find out the risk factors and take targeted prevention and control measures in these provinces.%目的 通过对2009年全国伤寒、副伤寒疫情及国家监测点监测结果分析,掌握疫情态势,了解高发地区病原构成、重点人群带菌状况以及菌株耐药变化情况,为防制对策提供依据.方法 用描述流行病学方法对网络直报的2009年伤寒、副伤寒疫情信息及国家监测点上报

  17. Chronic thyroiditis (Hashimoto disease)

    Science.gov (United States)

    Hashimoto thyroiditis; Chronic lymphocytic thyroiditis; Autoimmune thyroiditis; Chronic autoimmune thyroiditis; Lymphadenoid goiter - Hashimoto; Hypothyroidism - Hashimoto; Type 2 polyglandular autoimmune ...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Visualization of abscess formation in a murine thigh infection model of Staphylococcus aureus by 19F-magnetic resonance imaging (MRI.

    Directory of Open Access Journals (Sweden)

    Tobias Hertlein

    Full Text Available BACKGROUND: During the last years, (19F-MRI and perfluorocarbon nanoemulsion (PFC emerged as a powerful contrast agent based MRI methodology to track cells and to visualize inflammation. We applied this new modality to visualize deep tissue abscesses during acute and chronic phase of inflammation caused by Staphylococcus aureus infection. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, a murine thigh infection model was used to induce abscess formation and PFC or CLIO (cross linked ironoxides was administered during acute or chronic phase of inflammation. 24 h after inoculation, the contrast agent accumulation was imaged at the site of infection by MRI. Measurements revealed a strong accumulation of PFC at the abscess rim at acute and chronic phase of infection. The pattern was similar to CLIO accumulation at chronic phase and formed a hollow sphere around the edema area. Histology revealed strong influx of neutrophils at the site of infection and to a smaller extend macrophages during acute phase and strong influx of macrophages at chronic phase of inflammation. CONCLUSION AND SIGNIFICANCE: We introduce (19F-MRI in combination with PFC nanoemulsions as a new platform to visualize abscess formation in a murine thigh infection model of S. aureus. The possibility to track immune cells in vivo by this modality offers new opportunities to investigate host immune response, the efficacy of antibacterial therapies and the influence of virulence factors for pathogenesis.

  1. 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.

  2. Molecular cloning and chromosome assignment of murine N-ras.

    OpenAIRE

    Ryan, J.; Hart, C P; Ruddle, F H

    1984-01-01

    The murine N-ras gene was cloned by screening an EMBL-3 recombinant phage library with a human N-ras specific probe. Hybridization of two separate unique sequence N-ras probes, isolated from the 5' and 3' flanking sequences of the murine gene, to a mouse-Chinese hamster hybrid mapping panel assigns the N-ras locus to mouse chromosome three.

  3. Effectiveness of health education on typhoid and paratyphoid fever among primary and junior school students in township%乡镇中小学生伤寒副伤寒健康教育效果评价

    Institute of Scientific and Technical Information of China (English)

    孟宪鹏; 黎慕

    2013-01-01

    Objective To evaluate the effectiveness of typhoid and paratyphoid fever health education among rural schools and to provide basis on infectious disease health education among rural areas. Methods Students from 9 schools in 3 towns of high incidence rate of typhoid and paratyphoid fever were randomly selected, who had received typhoid and paratyphoid fever health education. Knowledge, attitude and behavior related with typhoid and paratyphoid fever were compared before and after health education. Results After intervention, the awareness rates of typhoid and paratyphoid fever knowledge, holding rates of related attitudes and behaviors among primary (70. 68% , 87. 95% , 19. 18% ) and junior school students (73. 62% , 90. 69% , 21. 72% ) were obviously higher than the baseline investigation( P <0.05). Before intervention, the awareness rates of typhoid and paratyphoid fever knowledge and holding rates of related attitudes among primary school students were obviously lower than those of junior school students) P <0. 05 ) , however, the difference between the two groups were not significant after the intervention. Conclusion The knowledge, attitude and behavior related with typhoid and paratyphoid fever in primary and junior school students need to be improved, especially in areas with high incidence. Health education on typhoid and paratyphoid fever has quite substantial effects.%目的 评价乡镇中小学校开展伤寒副伤寒健康教育的效果,为在农村地区开展传染病健康教育提供依据.方法 采用分层随机抽样方法,抽取贵州省平坝县内伤寒副伤寒高发区3个乡镇9所学校的小学生和初中生进行健康教育,比较干预前后伤寒副伤寒知识、态度、行为改变情况.结果 干预后小学生的伤寒副伤寒防治知识知晓率、态度和行为持有率分别为70.68%,87.95%,19.18%,初中生为73.62%,90.69%,21.72%,均明显高于干预前(P值均<0.05).干预前小学生的知识

  4. Clinical analysis of multiple organ injury induced by typhoid and paratyphoid A%伤寒副伤寒并发多器官损害的临床分析

    Institute of Scientific and Technical Information of China (English)

    曾颖玲; 叶晓光

    2009-01-01

    目的 充分认识伤寒副伤寒并发症的多样性,为临床诊疗提供依据.方法回顾性分析我院自1994年1月至2008年12月收治的99例伤寒副伤寒病例多器官损害的分布情况.结果伤寒副伤寒病例.器官损害最多的是中毒性肝炎(61.6%),其次为心肌损害(38.3%),呼吸系统损害(10.1%),肾损害(6.1%),肠出血(3%).结论伤寒副伤寒容易引起多器官损害.应引起临床医师的重视.%Objective This study is to fully analyze the diversity of complications in typhoid and paratyphoid A in order to provide evidence for clinical diagnosis and treatment. Methods Ninety-nine clinical cases of typhoid and paratyphoid A treated in our hospital during 1994 to 2008 were also analyzed for the presence of multiple organ damages.Results In the case of typhoid and paratyphoid A, the most frequently complication is toxic hepatitis (61.6%), followed by cardiac damage (38.3%),damage of respiratory system (10.1%), renal lesion (6.1%) and enteroptotic (3%).Conclusions The clinicians should pay attention to multiple organ injury induced by typhoid and paratyphoid A.

  5. Study on the Homology of Salmonella typhi Identified in Two Typhoid Outbreaks%两起伤寒沙门菌感染暴发流行病原的相似度研究

    Institute of Scientific and Technical Information of China (English)

    张婷; 李国民; 杨继先; 陆洲

    2013-01-01

    Objective To isolate, identify and genotype the Salmonella typhi identified in two typhoid outbreaks by pulse field gel electropherosis (PFGE), and to analyze their homology, so as to provide scientific basis for typhoid prevention and control. Methods The biochemistry and serology of 11 Salmonella typhi strains from two typhoid outbreaks were checked by traditional methods. The whole genome DNA fingerprints of the confirmed strains were analyzed by PFGE. Results Three banding patterns appeared in the maps of PFGE of 11 Salmonella typhi strains. Conclusions The two typhoid outbreaks are caused by different Salmonella typhi subtypes.%目的 应用脉冲场凝胶电泳(PFGE)技术对两起由伤寒沙门菌引起的聚集性暴发流行中所分离到的伤寒沙门菌进行分离鉴定和基因分型,对其病原进行同源性分析和分子流行病学探讨,为科学防治提供实验室检测依据. 方法 用传统方法对11株伤寒沙门菌菌株进行生化、血清学复核鉴定.对确认的伤寒沙门菌菌株,采用脉冲场凝胶电泳技术分析电泳酶切指纹图谱. 结果 11株伤寒沙门菌经PFGE,根据其条带的差异可分为3个PFGE型别. 结论 两起伤寒沙门菌感染为不同亚型所致.

  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. 伤寒副伤寒传播的风险因素及防控措施%Risk factors for the transmission of typhoid and paratyphoid fevers and prevention and control measures

    Institute of Scientific and Technical Information of China (English)

    阳波; 闫梅英; 阚飙

    2012-01-01

    伤寒副伤寒仍是部分国家比较严重的公共卫生问题,过去常常把这类疾病的传播途径混同于风险因素.本文对伤寒副伤寒暴发流行的风险因素做一综述,为伤寒副伤寒暴发流行采取有针对性的措施提供参考,也为查明暴发疫情的危险因素提供指示性线索.%Typhoid and paratyphoid fevers are still a serious public health problem in some countries. People used to confuse the transmission routes of the diseases and their risk factors. This paper attempts to summarize the transmission risk factors of typhoid and paratyphoid fevers in order to provide reference for the prevention and control of typhoid and paratyphoid fevers outbreak and suggest the identification of transmission risk factors.

  8. Rapid amplification of cDNA ends (RACE) improves the PCR-based isolation of immunoglobulin variable region genes from murine and human lymphoma cells and cell lines.

    Science.gov (United States)

    Doenecke, A; Winnacker, E L; Hallek, M

    1997-10-01

    The isolation of rearranged immunoglobulin (Ig) variable region (V) genes is usually performed by PCR with consensus primers binding to conserved regions within the V sequences. However, the isolation of Ig genes by this method is hampered in 15-35% by technical difficulties, mostly mismatches of oligonucleotide primers to V sequences. In order to obtain DNA sequences from V heavy chain (VH) genes which could not be amplified with consensus primers, we used a modified PCR technique, the rapid amplification of cDNA ends (RACE) PCR in combination with new heavy chain constant region primers for the isolation of human and murine VH genes. In comparison, consensus primer PCR with different sets of previously published oligonucleotide primers was used. Both methods were applied to isolate VH genes from murine B cell lymphoma (A20 and BCL1), myeloma (NS1) and hybridoma (SP6) cell lines and from freshly isolated human chronic lymphocytic leukemia and lymphoma cells. RACE PCR allowed the amplification and subsequent cloning of the complete VH gene in all cases. In contrast, consensus primer PCR failed to isolate the VH sequence of the murine A20 cell line; this was explained by a mismatch of consensus primers with VH sequences. When both PCR methods amplified VH sequences, the DNA sequences obtained were identical. Taken together, RACE PCR represents a reliable and versatile method for the isolation of VH genes from human and murine lymphoma cells, in particular if consensus primer PCR fails.

  9. Metabolic syndrome components in murine models.

    Science.gov (United States)

    Lawson, Heather A; Cheverud, James M

    2010-03-01

    Animal models have enriched understanding of the physiological basis of metabolic disorders and advanced identification of genetic risk factors underlying the metabolic syndrome (MetS). Murine models are especially appropriate for this type of research, and are an excellent resource not only for identifying candidate genomic regions, but also for illuminating the possible molecular mechanisms or pathways affected in individual components of MetS. In this review, we briefly discuss findings from mouse models of metabolic disorders, particularly in light of issues raised by the recent flood of human genome-wide association studies (GWAS) results. We describe how mouse models are revealing that genotype interacts with environment in important ways, indicating that the underlying genetics of MetS is highly context dependant. Further we show that epistasis, imprinting and maternal effects each contribute to the genetic architecture underlying variation in metabolic traits, and mouse models provide an opportunity to dissect these aspects of the genetic architecture that are difficult if not impossible to ascertain in humans. Finally we discuss how knowledge gained from mouse models can be used in conjunction with comparative genomic methods and bioinformatic resources to inform human MetS research.

  10. Proteomic analysis of normal murine brain parts.

    Science.gov (United States)

    Taraslia, Vasiliki K; Kouskoukis, Alexandros; Anagnostopoulos, Athanasios K; Stravopodis, Dimitrios J; Margaritis, Lukas H; Tsangaris, George Th

    2013-01-01

    Murine brain is an excellent tool for studying protein expression and brain function in mammals. Although mice are an extensively used model to recapitulate various pathological conditions, the proteome of the normal mouse brain has not been yet reported. In the present study, we identified the total proteins of different parts of the brain of CB7BL/6 mice, a widely used strain, by applying proteomic methodologies. The adult mouse brain was dissected anatomically into the following regions: frontal cortex, olfactory bulb, hippocampus, midbrain, cerebellum, hypothalamus and medulla. Total protein extracts of these regions were separated by two-dimensional gel electrophoresis and analyzed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, following in-gel digestion with trypsin. Protein identification was carried out by peptide mass fingerprint. Thus, 515 different single-gene products were identified in total, 54 expressed specifically in the olfactory bulb, 62 in the hippocampus, 36 in the frontal cortex, five in the cerebellum, nine in the midbrain, eight in the hypothamamus and 10 in the medulla. The majority of the proteins were enzymes, structural proteins and transporters. Moreover, the distribution of these molecules appears to exhibit direct correlation with the function of the brain regions where they were expressed. This study leads to the complete characterization of the normal mouse brain proteome as well as the protein expression profile of the different brain regions. These results will aid in addressing unmet scientific needs regarding physiological and pathological brain functions.

  11. 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.

  12. 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.

  13. Antitumor Activity and Immune Enhancement of Murine Interleukin-23 Expressed in Murine Colon Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Baoen Shan; Jingsheng Hao; Qiaoxia Li; Masatoshi Tagawa

    2006-01-01

    Interleukin (IL)-23, a cytokine composed of p19 and the p40 subunit of IL-12, can enhance the proliferation of memory T cells and production of IFN-γ from activated T cells. It can also induce antitumor effects in murine model. To further evaluate the antitumor activity and immune enhancement of IL-23 in vivo, murine colon carcinoma cells retrovirally transduced with mIL-23 gene were injected subcutaneously (s.c.) into BALB/c mice.Survival time and tumor volume were observed. LDH release assay, [3H]-TdR incorporation assay and ELISA were used to determine CTL activity, proliferation of splenocytes and level of cytokines, respectively. Number of dendritic cells (DCs) was analyzed by flow cytometry (FCM). IL-23 secreted by Colon26/IL-23 cells suppressed the growth of tumor and prolonged the survival time of mice, enhanced proliferation of splenocytes, CTL activity, and number of DCs. IL-23 also promoted the production of Th1 cytokines such as IFN-γ, IL-12 and TNF-o. However,the level of IL-4 was not enhanced significantly. These data suggested that IL-23 secreted by tumor cells can induce antitumor activity by enhancing immune response.

  14. 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...

  15. 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...

  16. 郴州市2005~2012年伤寒副伤寒流行特征分析%Analysis on epidemiological features of typhoid and paratyphoid fever from 2005 to 2012 in Chenzhou

    Institute of Scientific and Technical Information of China (English)

    刘卫; 刘晓峰; 朱韩武; 李成华

    2014-01-01

    目的:分析郴州市2005~2012年伤寒副伤寒流行趋势,为制定伤寒副伤寒防控措施提供科学依据。方法采用描述性流行病学方法分析郴州市近8年伤寒副伤寒疫情情况。结果郴州市2005~2012年共报告伤寒副伤寒1062例,发病率为1.61~6.70/10万,呈逐年下降趋势;发病以农民、学生和儿童为主,年龄集中在50岁以下,地区分布上表现为相对集中趋势。结论郴州市2005~2012年伤寒副伤寒发病呈逐年下降趋势,部分高发地区发病下降迅速。但需加强对农民、学生和儿童等高危人群的健康教育,改善农村地区卫生条件和加强疫情监测,进一步降低伤寒副伤寒发病率。%Objective The study was to analyze the epidemic trend of typhoid and paratyphoid fever from 2005 to 2010 in Chenzhou so as to provide scientific basis for the disease control and prevention .Methods Descriptive epidemiological study was used to analyze the epidemic situation of typhoid and paratyphoid fever in the recent 8 years throughout Chenzhou .Results 1 062 cases of typhoid and paratyphoid fever were reported in Chenzhou from 2005 to 2012 ,and the incidence is 1 .61~6 .70 per 100 ,000 ,showed a downtrend year by year .The main pa-tients are farmers ,students and children ,concentrated in people who were younger than 50 ,and regional distri-bution characterized by relatively concentrated trend . Conclusion Typhoid and paratyphoid fever in Chenzhou show a decreasing trend from 2005 to 2012 ,and the rates of the disease in part of high -prevalence areas de-creased rapidly .However ,we should strengthen the health education of high -risk groups and the epidemic moni-toring ,and improve health conditions in rural areas to reduce the incidence of typhoid and paratyphoid fever .

  17. 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

  18. Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

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    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.

  19. 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.

  20. 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.

  1. Isotype specific immune responses in murine experimental toxocariasis

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    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.

  2. Comparisons of epidemic features of typhoid and paratyphoid A in Guangxi, 2004- 2010%2004-2010年广西伤寒与甲型副伤寒流行特征对比分析

    Institute of Scientific and Technical Information of China (English)

    李永红; 林玫; 廖和壮

    2012-01-01

    Objective To compare the epidemic features of typhoid and paratyphoid A in Guangxi. Methods The distributional features of time, region and population of typhoid and paratyphoid A were compared by analyzing infectious disease reporting data from 2004 to 2010 in Guangxi. Results The annual reporting incidence rates of typhoid and paratyphoid A in Guangxi both had a parallel downtrend. Both incidence curves were similar, with the peak incidence of typhoid and paratyphoid A in July and August, respectively. Both diseases showed dominant regional features, and the two diseases were highly relevant in terms of regions ( r=0.938, P<0.001). Even though males were more than females in both diseases, their incidence rates were very similar. Among different ages, the incidence rates of typhoid were similar, whereas the incidence age of paratyphoid A culminated at 5 to 30 years old. Peasants, students, scattered children and workers topped the occupation list of both diseases, with peasants topping of typhoid and students topping of paratyphoid A. Conclusions As the prevention and control of typhoid and paratyphoid A are concerned, emphasis should be focused on countryside and school, and both are to be strengthened in the standardized treatment and management of patients.%目的 了解广西伤寒与甲型副伤寒流行特征的异同点,为有效防控伤寒与甲型副伤寒提供科学依据.方法 利用2004 - 2010年广西传染病报告数据,分析伤寒与甲型副伤寒的时间、地区及人群分布特征.结果 广西伤寒与甲型副伤寒的年报告发病率基本呈平行下降趋势,发病高峰分别在每年7月和8月,后者晚1个月,两者发病曲线相似;二者呈现明显地区流行特征,且地区分布具有高度相关性(r=0.938,P<0.001);两病病例男性均多于女性,但发病率很接近;伤寒在各年龄段人群的发病率较为均衡,甲型副伤寒则以5~30岁年龄段人群发病率较高;两病病例均以农民、

  3. Epidemiological analysis on typhoid fever in Kashi Prefecture from 2005-2010%喀什地区2005-2010年伤寒疫情流行病学分析

    Institute of Scientific and Technical Information of China (English)

    王庭宇; 党江安; 李朝霞; 王立杰; 胥丽敏

    2012-01-01

    [Objective]To investigate the epidemic causes and characteristics of typhoid fever, and provide evidence for developing control measures. [ Methods]The epidemic data of typhoid fever was analyzed by using descriptive epidemiology in Kashi Prefecture from 2005-2010. The incidence trend described. [Results] A total of 3 267 cases of typhoid fever was reported through direct network report, with average annual incidence rate of 14.33/100 000. The epidemic of typhoid fever showed obviously seasonal characteristics, with peak incidence in August- October. But sporadic cases appeared in other months. Then the total situation showed a decreasing trend in the 6 years, but the incidence fluctuated at a high level. The positive rate of typhoid was 14.47% from monitoring and was extremely low in focus groups and outside environment and the typhoid bacterium was the main strain type. [Conclusion]The important and main reasons for the typhoid fever outbreak are the polluted water resources, poor sanitation, bad living habits, low immunity, ineffective segregation and daily contact transmission.%目的 调查分析喀什地区伤寒疫情的流行原因和特征,为采取控制措施提供依据.方法 利用描述流行病学方法,对喀什地区2005-2010年伤寒疫情进行分析,描述伤寒6年发病率的变化趋势.结果 2005-2010年喀什地区共通过网络直报报告伤寒病例3 267例,年平均发病率约为14.33/10万.存在明显的季节集中趋势,发病高峰为8-10月份,其他月份均有不同程度的散发病例.6年期间伤寒发病率总体呈现下降趋势,但是在较高发病率上波动.伤寒病例监测阳性率为14.47%,重点人群和外环境监测阳性率极低;菌株分型以伤寒为主.结论 饮用不安全饮水是发生伤寒暴发流行的重要原因,卫生条件差,不良的生活习惯,人群免疫力低,传染源得不到及时有效的隔离治疗,日常接触传播等是该区伤寒流行的主要因素.

  4. METEOROLOGICAL EPIDEMIOLOGICAL CHARACTERISTICS ON ONSET OF TYPHOID FEVER IN HANDAN%邯郸市伤寒发病的气象流行病学特征分析

    Institute of Scientific and Technical Information of China (English)

    邓健; 果丽平; 李燕霞

    2014-01-01

    Objective To look for the scientific method which could apply to research the relationships between typhoid fever incidence and meteorological factors,and to discuss the meteorological epidemiology characteristics of typhoid fever.Methods The data of typhoid fever, meteorological parameters and population in 1991-2010 in Handan were collected and analyzed. Results ①Collinearity diagnosis of meteorological parameters showed that the minimal tolerance was 0.014 and the maximal variance inflation factor was 73.264.②Monthly incidence of typhoid fever had significant positive correlation with monthly mean temperature,monthly extreme minimum temperature,monthly extreme maximum temperature,monthly small evaporation, monthly total precipitation,monthly sunshine hours and monthly average relative humidity,and significant negative correlation with monthly average air pressure by using Spearman correlation analysis (P<0.05 or <0.01 ).The correlation coefficient of typhoid fever and monthly mean temperature was the biggest(rs=0.592).③The result of KMO and Bartlett showed that test of meteorological parameters was very suitable for factor analysis.Conclusion The problem of multicollinearity in 10 meteorological parameters was very serious.Monthly mean temperature was the main meteorological factor influencing typhoid fever incidence.The non natural water factor was the main factor affecting typhoid fever incidence.%目的:查找适用于研究伤寒发病率和气象因素之间关系的科学方法,探讨邯郸市伤寒的气象流行病学特征。方法收集1991-2010年邯郸市伤寒疫情资料、气象资料和人口资料,对数据进行统计分析。结果①气象参数的共线性诊断结果显示,本组气象因子数据容差最小为0.014,方差膨胀因子最大达73.264。②采用Spearman相关分析结果显示,伤寒月发病率与月平均气温、月极端最低气温、月极端最高气温、月小型蒸发量、月总降雨量、

  5. Chronic inflammatory demyelinating polyneuropathy

    Science.gov (United States)

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... Health care providers also consider CIDP as the chronic form of Guillain-Barré syndrome. The specific triggers ...

  6. Dealing with chronic cancer

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000933.htm Dealing with chronic cancer To use the sharing features on this ... be controlled for a period of time. Controlling Chronic Cancer When you have a chronic cancer, the ...

  7. 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....

  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. 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.

  10. Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.

    Science.gov (United States)

    Lokken, Kristen L; Mooney, Jason P; Butler, Brian P; Xavier, Mariana N; Chau, Jennifer Y; Schaltenberg, Nicola; Begum, Ramie H; Müller, Werner; Luckhart, Shirley; Tsolis, Renée M

    2014-05-01

    Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection.

  11. Association between use of proton pump inhibitors and non-typhoidal salmonellosis identified following investigation into an outbreak of Salmonella Mikawasima in the UK, 2013.

    Science.gov (United States)

    Freeman, R; Dabrera, G; Lane, C; Adams, N; Browning, L; Fowler, T; Gorton, R; Peters, T; Mather, H; Ashton, P; Dallman, T; Godbole, G; Tubin-Delic, D; Charlett, A; Fisher, I; Adak, G K

    2016-04-01

    In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0-38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage.

  12. 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.

  13. 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.

  14. 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.

  15. Mouse models to assess the efficacy of non-typhoidal Salmonella vaccines: revisiting the role of host innate susceptibility and routes of challenge

    Science.gov (United States)

    Simon, Raphael; Tennant, Sharon M.; Galen, James E.; Levine, Myron M.

    2011-01-01

    Non-typhoidal Salmonella enterica (NTS) serovars Typhimurium and Enteritidis are important causes of bacterial gastroenteritis in the USA and worldwide. In sub-Saharan Africa these two serovars are emerging as agents associated with lethal invasive disease (e.g., bacteremia, meningitis). The development of NTS vaccines, based on mucosally-administered live attenuated strains and parenteral non-living antigens, could diminish the NTS disease burden globally. Mouse models of S. Typhimurium and S. Enteritidis invasive disease can accelerate the development of NTS vaccines. Live attenuated NTS vaccines elicit both cellular and humoral immunity in mice and their efficacy is well established. In contrast, non-living vaccines that primarily elicit humoral immunity have demonstrated variable efficacy. An analysis of the reported studies with non-living vaccines against S. Typhimurium and S. Enteritidis reveals that efficacy is influenced by two important independent variables: 1) the innate susceptibility to NTS infection that differs dramatically between commonly used mouse strains and, 2) the virulence of the NTS strain used for challenge. Protection by non-living vaccines has generally been seen only in host-pathogen interactions where a sub-lethal infection results, such as challenging resistant mice with either highly virulent or weakly virulent strains or susceptible mice with weakly virulent strains. The immunologic basis of this discrepancy and the implications for human NTS vaccine development are reviewed herein. PMID:21616112

  16. 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.

  17. 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).

  18. Typhoid fever with severe abdominal pain: diagnosis and clinical findings using abdomen ultrasonogram, hematology-cell analysis and the Widal test.

    Science.gov (United States)

    Arjunan, Maripandi; Al-Salamah, Ali A

    2010-10-04

    A six-year-old boy with high-grade fever and abdominal pain in the epigastric region was examined with ultrasonogram of the abdomen. Hematology-cell analysis, serology (Widal test), urine analysis, and blood cultures were also performed. The ultrasonogram was helpful for the identification of multiple organ involvement with Salmonella typhi. The results revealed mild hepatosplenomegaly, minimal ascitis, and mesenteric lympoadenopathy. Hematological analysis showed a white blood count of 6,300 cells mL-1; a red blood cell count of 4.54 million/cu mm. The erythrocyte sedimentation rate (ESR) was 24 mm/1 hr; hemoglobin level of 11.5 g/dl; and a platelet count of 206,000 cells/mL. The patient's serum was agglutinated with lipopolysaccharide (TO), the titre value was 1:320 dilution, and flagellar antigen (TH) titre was 1:640. The patient was diagnosed with typhoid fever. Ceftriaxone was given intravenously for five days and the patient fully recovered.

  19. 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.

  20. Mutational dynamics of murine angiogenin duplicates

    Directory of Open Access Journals (Sweden)

    Fares Mario A

    2010-10-01

    Full Text Available Abstract Background Angiogenin (Ang is a protein involved in angiogenesis by inducing the formation of blood vessels. The biomedical importance of this protein has come from findings linking mutations in Ang to cancer progression and neurodegenerative diseases. These findings highlight the evolutionary constrain on Ang amino acid sequence. However, previous studies comparing human Angiogenin with homologs from other phylogenetically related organisms have led to the conclusion that Ang presents a striking variability. Whether this variability has an adaptive value per se remains elusive. Understanding why many functional Ang paralogs have been preserved in mouse and rat and identifying functional divergence mutations at these copies may explain the relationship between mutations and function. In spite of the importance of testing this hypothesis from the evolutionarily and biomedical perspectives, this remains yet unaccomplished. Here we test the main mutational dynamics driving the evolution and function of Ang paralogs in mammals. Results We analysed the phylogenetic asymmetries between the different Ang gene copies in mouse and rat in the context of vertebrate Ang phylogeny. This analysis shows strong evidence in support of accelerated evolution in some Ang murine copies (mAng. This acceleration is not due to non-functionalisation because constraints on amino acid replacements remain strong. We identify many of the amino acid sites involved in signal localization and nucleotide binding by Ang to have evolved under diversifying selection. Compensatory effects of many of the mutations at these paralogs and their key structural location in or nearby important functional regions support a possible functional shift (functional divergence in many Ang copies. Similarities between 3D-structural models for mAng copies suggest that their divergence is mainly functional. Conclusions We identify the main evolutionary dynamics shaping the variability of

  1. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2010-12-01

    Full Text Available 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 InlAm*. 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 InlAm* 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Murine Sirt3 protein isoforms have variable half-lives

    Science.gov (United States)

    Sirt3 is a NAD+-dependent protein deacetylase mainly localized in mitochondria. Recent studies indicate that the murine Sirt3 gene expresses different transcript variants resulting in three possible Sirt3 protein isoforms with variable lengths at the N-terminus: M1 (aa 1-334), M2 (aa 15-334), and M3...

  7. 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

  8. Macropinocytosis is the Entry Mechanism of Amphotropic Murine Leukemia Virus

    DEFF Research Database (Denmark)

    Rasmussen, Izabela; Vilhardt, Frederik

    2015-01-01

    The entry mechanism of murine amphotropic retrovirus (A-MLV) has not been unambiguously determined. We show here that A-MLV does not internalize by caveolae or other pinocytic mechanism, but by macropinocytosis. Thus A-MLV infection of mouse embryonic fibroblasts deficient for caveolin or dynamin...

  9. Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies

    DEFF Research Database (Denmark)

    Jensen, H.E.; Aalbaek, B.; Lind, Peter

    1996-01-01

    Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with h...... for the in situ diagnosis of systemic bovine zygomycosis....

  10. Expression of biologically active murine interleukin-18 in Lactococcus lactis.

    Science.gov (United States)

    Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

    2016-11-01

    The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL(-1) and 0.6-0.7 ng mL(-1), respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces.

  11. 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...

  12. 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...

  13. Correlation between incidence of typhoid fever and climate changes in Beijing from the perspective of Six-qi%从六气角度探讨北京地区伤寒与气象变动的相关性

    Institute of Scientific and Technical Information of China (English)

    黄羚; 刘柳青; 宋娜; 吕智燚; 刘张博方; 贺娟

    2014-01-01

    Objective To investigate the correlation between incidence of typhoid fever and climate changes in Beijing from the perspective of Six -qi.Methods Meteorological data and clinical data were collected in Beijing from 1985 to 2004 including:average temperature , water-vapor pressure , relative humidity , precipitation and wind speed.Each year was divided into six stages from the perspective of Six -qi theory.Correlation between incidence of typhoid fever and climate changes was analyzed with SPSS 19.0 in method of one-factor ANOVA and multiple linear regression.Results The outcome number of typhoid fever in the third stage was larger than other stages .The inci-dence of typhoid fever was positively correlated with average temperature , relative humidity, water-vapor pressure andprecipitation,thecorrelationwasstatisticallysignificant(P<0.05).Conclusion :Theincidenceoftyphoid fever in Beijing was correlated with climate changes .Different meteorological factors inordinately influenced the inci-dence of typhoid fever .It is feasible to predict the prevalence of typhoid fever by using the meteorological data in pre -vious year .%目的:根据中医运气学说理论,从六气角度探讨伤寒发病与气象变动的相关性,讨论各气象因素对伤寒发病的影响。方法回顾北京市1985-2004年907例伤寒发病人数及相应的气象资料,包括平均气温、平均降水量、平均湿度、平均水汽压及平均风速。将各气象因子与伤寒发病数据按六气分段进行相关性分析。分别将前一年和当年的气象资料与伤寒发病人数进行单因素相关分析,将相关性较高的气象因子纳入多元逐步回归方程,建立回归模型,比较二者的关联性。结果终之气、初之气为伤寒低发时期,三之气和四之气期间为高发时期,三之气最高。伤寒的发病与前一年平均气温、平均降水量、平均湿度、平均水汽压呈正相关,与

  14. 贵州省伤寒副伤寒高发地区综合防治%Comprehensive Prevention and Control of Typhoid/Paratyphoid in High Incidence Area in Guizhou Province

    Institute of Scientific and Technical Information of China (English)

    唐光鹏; 张静; 刘发文; 孙军玲; 姚光海; 田克诚; 王定明; 王子军; 王小力

    2011-01-01

    Objective To discuss the prevention and control of typhoid/paratyphoid in area with high incidence,and provide scientific evidence for the large scale prevention and control of the disease. Methods Fever patient surveillance was conducted to find typhoid/paratyphoid patients timely. Standard management of infectious disease, disinfection of source water and health education were conducted in intervention area to reduce the incidence of typhoid/paratyphoid. Results The detection rate of active search of suspected patients was 0. 08% ,the detection rate of active surveillance of suspected patients among fever patients was 0. 33%. Twelve S. typhoid strains were isolated from 319 fever patients, the detection rate was 3. 76% . The incidence of typhoid/paratyphoid in inten ention area decreased by 60. 06% compared with the control area and by 71. 2% compared with the period before intervention. Conclusion Conducting surveiUance of fever patients by timely blood cuhure is essential for the early detection of typhoid/paratyphoid infectious source. The epidemic could be controlled by the standard treatment of infectious patients, interruption of infectious route and protecting susceptible population.%目的 对伤寒副伤寒高发区开展综合防治,以摸索贫困地区伤寒副伤寒防制经验,为开展大规模的防治工作提供科学依据.方法 通过建立发热患者监测,以及时发现患者,在干预区实施对传染病规范管理,对重点水源消毒管理,开展健康教育等措施,以降低伤寒副伤寒发病率.结果 主动搜索疑似伤寒副伤寒发现率0.08%,主动发热就诊病例监测,疑似伤寒副伤寒病例发现率0.33%;对3664例发热就诊病例采血319例作伤寒沙门菌培养,检出伤寒沙门菌12株,伤寒副伤寒阳性率3.76%.干预区伤寒副伤寒发病率比对照区下降60.06%%,比干预前发病率下降71.2%.结论 开展就诊发热病例监测,及时采血培养,是早期发现伤寒副伤寒

  15. 2008~2010年开阳县伤寒、副伤寒监测结果分析%Analvsis of results of typhoid and paratyphoid surveillance in Kaivang, 2008-2010

    Institute of Scientific and Technical Information of China (English)

    蒋国书; 唐云义; 刘明强; 陈晓琴; 刘俊伦; 张春芳

    2011-01-01

    目的 掌握开阳县伤寒、副伤寒疾病的流行情况,探寻危险因素,为提出有针对性的综合性防制措施提供依据.方法 在开阳县选择既往发病较多的6个乡镇建立以全人群的伤寒、副伤寒病原菌监测系统,对就诊发热病例进行登记、采血作病原学检测,监测时间2008年5月~2010年8月. 结果 登记发热病例112 503例,采集血液标本8 529份,检出阳性病例92例,其中伤寒1例,副伤寒91例.病例以10~40岁人群为主,农民占确诊病例数的69.57%;体温在37.5~38.0℃的占52.17%,症状多以上感症状为主. 结论 开阳县流行的菌株主要为甲型副伤寒;加强对发热人群伤寒、副伤寒监测,早期发现、及时治疗病人是伤寒、副伤寒防控的重要措施.%Objective To ascertain the prevalence of typhoid and paratyphoid fever in Kaiyang and explore risk factors for both in order to provide a basis for targeted comprehensive control measures. Methods Six towns in Kaiyang with a higher incidence of typhoid and paratyphoid fever were selected, and a system was established to monitor bacteria causing typhoid and paratyphoid fever. Cases of fevers were registered and blood was collected for pathogen detection. Monitoring took place from May 2008 to August 2010. Results Blood samples were collected from 8 529 patients among 112 503 registered cases of fevers. Of these patients, 92 tested positive, including 1 case of typhoid fever and 91 cases of paraty-phoid fever. Patients were mainly ages 10 to 40, and farmers accounted for 69. 57% of confirmed cases. Of the patients, 52. 17% had a temperature of 37. 5 - 38. 0℃. Many patients had multiple subjective symptoms. Conclusion The prev-alent strain in Kaiyang was mainly Paratyphoid A. Enhancing surveillance of people with typhoid fever and paratyphoid fever, early detection, and timely treatment of patients are crucial to prevention and control of typhoid and paratyphoid fe-vers.

  16. 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

    -β1-induced glomerular basement membrane thickening is not shown. The amount and distribution profile of MMP-2 may suggest a role of the enzyme herein. We conclude that Smad3 targeting is not exclusively beneficial as Smad3 has diverse transcriptional regulatory effects in different cell types...

  17. 新疆莎车县1起伤寒暴发疫情的流行病学分析%Epidemiological Analysis on an Outbreak of Typhoid in Shache County of Xinjiang

    Institute of Scientific and Technical Information of China (English)

    党江安; 宿新农; 李朝霞; 王立杰; 卡日曼; 李光明; 王建军

    2011-01-01

    目的 通过对莎车县伤寒暴发疫情的流行病学分析,为查明暴发原因和采取控制措施提供科学依据.方法 采用现场调查的方法.结果 莎车县伤寒疫情共报告病例253例,发病率为31.63/10万,发病年龄主要集中在20岁以下年龄组,此年龄组占总病例的72.33%.结论 该次伤寒暴发疫情主要是因为饮用被污染的自来水,同时也存在食用冰水、凉皮等三凉食品,病家卫生条件差,苍蝇密度高,日常生活接触传播,农民自我保健意识差等多种原因.%[Objective]With the epidemiological analysis of typhoid outbreak in Shache county, to provide the scientific basis for finding out the causes of outbreak and carrying out the control measures.[Methods]The field investigation was adopted.[Results]253 cases of typhoid were reported in Shache county, and the incidence was 31.63/lakh.72.33% of patients were people under 20 years old.[Conclusion]This typhoid outbreak was mainly caused by drinking the contaminated tap water, meanwhile, there were other causes which included drinking ice-water, eating cold starch noodle, poor sanitary conditions of families, high flies population density, daily contact transmission and poor self health care consciousness of peasants.

  18. 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.

  19. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

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    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.

  20. 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.

  1. [Chronic otitis mediaChronic Otitis Media].

    Science.gov (United States)

    Kohles, N; Schulz, T; Eßer, D

    2015-11-01

    There are 2 different kinds of chronic otitis media: Otitis media chronica mesotympanalis and otitis media chronica epitympanalis (cholesteatoma). The incidence of chronic otitis media as reported in literature differs in a wide range. The incidence rates vary between 0.45 and 46%. Both, otitis media chronica mesotympanalis and cholesteatoma, lead to eardrum perforation due to lengthy and recurring inflammations. Furthermore, chronic otitis media is characterized by frequently recurring otorrhea and conductive hearing loss.

  2. 2005-2011年江阴市伤寒副伤寒流行特征分析%Analysis on epidemiological characteristics of typhoid and paratyphoid in Jiangyin City from 2005-2011

    Institute of Scientific and Technical Information of China (English)

    姚建香; 马焰; 葛备; 束芳燕

    2013-01-01

    [Objective] To analyze the epidemiological characteristics and tendency of typhoid and paratyphoid in Jiangyin City from 2005-2011, provide the basis for making prevention and control measures. [Methods]The epidemic data and monitoring results in Jiangyin City from 2005-2011 were statistically analyzed with descriptive epidemiological method. [Results]The average incidence rate of typhoid and paratyphoid in Jiangyin City from 2005-2011 was 1. 41/lakh, and the peak season was April to October. Most of cases were young adults aged 15-49 years old, and 0-5 year-old age group also accounted for a great proportion. Students, farmers and scattered children were the high-risk population, and areas with high incidence rate were floating population concentrated towns. [Conclusion]The epidemic situation of typhoid in Jiangyin City has been maintained at a relatively low level, but there is still a possibility of recovery. So it is necessary to strengthen the health education among the high-risk population (including students, farmers, scattered children and floating population) , improve the monitoring, to reduce the incidence rate of typhoid and paratyphoid.%目的 分析2005-2011年江阴市伤寒副伤寒流行特征和趋势,为制定防治策略提供依据.方法 采用描述流行病学分析方法对江阴市2005-2011年疫情资料和监测点结果进行统计分析.结果 2005-2011年江阴市伤寒副伤寒年平均发病率为1.41/10万,发病高峰为4-10月,病例以15 ~49岁青壮年为主,0~5岁年龄组也占较高比例,学生、农民、散居儿童为高危人群,高发地区为流动人口比较集中的乡镇.结论 江阴市伤寒疫情稳定在较低水平,但仍然面临回升的可能,仍需采取对学生、农民、散居儿童和流动人口等高危人群加强健康教育,继续加强疾病监测工作等综合性防控措施来进一步降低伤寒副伤寒发病率.

  3. Study on Incidence of Typhoid Fever and Paratyphoid Fever with Seasonal Trend Model%全国伤寒、副伤寒发病的季节趋势模型研究

    Institute of Scientific and Technical Information of China (English)

    郭海强; 刘红波; 曲波; 孙高

    2011-01-01

    目的 分析全国2006-2010年伤寒、副伤寒报告病例数据,应用季节趋势模型预测2011年的发病例数.方法 应用SPSS 15.0和Excel软件拟合2006-2010年全国伤寒、副伤寒逐月报告发病人数的季节趋势模型.结果 全国伤寒、副伤寒的发病情况呈逐年下降趋势,应用逐月报告发病人数建立的季节趋势模型差异有统计学意义(F=11.688,P=0.001).应用模型预测2011年全国伤寒、副伤寒的发病人数为12 543例,较上年减少2 169例.结论 季节趋势模型充分考虑了疾病流行的长期趋势和季节性流行特点,拟合近年全国伤寒、副伤寒发病数据效果较好,可利用模型进行短期预测.%Objective To explore the reported incidence data of typhoid fever and paratyphoid fever in China from 2006 to 2010 by fitting a seasonal trend model, and to predict the incidence of the diseases in 2011 with the established model.Methods SPSS 15.0 and Excel XP were applied to fit the seasonal trend model on the incidence of typhoid fever and paratyphoid fever. Results Tho reported cases of typhoid fever and paratyphoid fever declined annually during the period of 2006~2010, and the difference was statistically significant ( F = 11. 688, P = 0. 001 ). With tho established seasonal trend model, the predictive cases of the diseases in 2011 would be 12,543, which are 2,169 less than those of 2010. Conclusions The long- term epidemic trend and seasonal epidemic character are all taken into account in the seasonal trend model. Tho fitted result of the established model is acceptable on the incidence of typhoid fever and paratyphoid fever, and the model can be applied to predict future short - term incidence.

  4. 1990-2009年岱山县伤寒副伤寒的流行病学特征%Epidemiological features of typhoid and paratyphoid fever in Daishan county, Zhejiang, 1990-2009

    Institute of Scientific and Technical Information of China (English)

    何存弘

    2011-01-01

    目的 了解和掌握岱山县1990-2009年的伤寒、副伤寒流行规律,分析流行因素,探讨防制对策.方法 对岱山县1990-2009年伤寒副伤寒疫情监测资料进行流行病学调查分析.结果 1990-2009年岱山县共报告伤寒、副伤寒病人721例,无死亡病例,年平均发病率为17.26/10万,2002年以后发病率逐渐下降,发病率均在10/10万以下.发病具有明显的夏、秋季高峰;发病年龄主要集中在20~40岁年龄段,占72.86%(524/721);男性明显高于女性;渔船民是主要的发病人群.结论 应加强对群众,尤其是渔船民的健康教育.加强包括海水产品在内的综合性监测工作,控制伤寒副伤寒的暴发流行.%Objective To analyze the epidemiological features of typhoid and paratyphoid fever in Daishan county and explore the measures of disease prevention and control.Methods A descriptive epidemiological analysis was used for analyzing the surveillance data of typhoid and paratyphoid fever in Daishan county, Zhejiang province, from 1990 to 2009.Results 721 cases of typhoid and paratyphoid fever were reported in Daishan county for the period with no deaths.The average annual incidence rate was 17.26/lakh, which decreased to less than 10/lakh after the year of 2002.The seasonal peak incidences appeared in summer and autumn.72.68% (524/721) of cases occurred at age group of 20-40 years.Fishermen had higher incidence rate than that in the residents of other occupations.The incidence rate was higher in men than that in women.Conclusion It is important to provide the education of hygienic behaviors to local residents, especially fishermen.Public health surveillance should be strengthened to control the outbreak of typhoid and paratyphoid fever.

  5. Epidemic Status of Typhoid Fever and Paratyphoid Fever in Yunnan Province from 2008 to 2010%云南省2008一2010年伤寒副伤寒发病情况

    Institute of Scientific and Technical Information of China (English)

    黄玉芬; 刘志涛

    2011-01-01

    目的 掌握近年来云南省伤寒副伤寒的流行病学特征,为制定有效的预防控制措施提供科学依据.方法应用描述流行病学方法对云南省各州(市)2008-2010年的伤寒副伤寒疫情年报数据进行分析.结果云南省2008-2010年共报告伤寒副伤寒病例14675例,死亡3例;年平均发病率为10.77/10万,年平均死亡率为0.002/10万.西双版纳州、玉溪市、德宏州、红河州、昆明市及保山市6个州(市)为云南省的高发地区,5-10月为高发月份(64.66%),发病年龄以20~39岁组居多,农民和学生为高发人群(64.65%).结论云南省伤寒副伤寒发病率处于较高水平,应采取综合性的预防控制措施.%[Objective] To understand the epidemiological characteristics of typhoid fever and paratyphoid fever in Yunnan province in the recent years, provide scientific evidence for making effective prevention and control measures. [Methods]The annual reports of typhoid fever and paratyphoid fever in all prefectures (cities) of Yunnan province from 2008 to 2010 were analyzed with descrip-tive epidemiological method. [Results] 14 675 cases of typhoid fever and paratyphoid fever were reported in Yunnan province from 2008 to 2010, and 3 patients died of the disease. The average annual incidence was 10.77/lakh, and average annual mortality was 0.002/lakh. Xishuangbanna prefecture, Yuxi city, Dehong prefecture, Honghe prefecture and Kunming city had the high incidence of the disease. The peak season was from May to October (64. 66% ). A majority of cases occurred in people aged 20 ~ 39 years old, and most of patients were farmers and students (64.65% ). [Conclusion]The incidence of typhoid fever and paratyphoid fever is high in Yunnan province, and it is necessary to carry out the comprehensive prevention and control measures.

  6. A comparison of non-typhoidal Salmonella from humans and food animals using pulsed-field gel electrophoresis and antimicrobial susceptibility patterns.

    Directory of Open Access Journals (Sweden)

    Carol H Sandt

    Full Text Available Salmonellosis is one of the most important foodborne diseases affecting humans. To characterize the relationship between Salmonella causing human infections and their food animal reservoirs, we compared pulsed-field gel electrophoresis (PFGE and antimicrobial susceptibility patterns of non-typhoidal Salmonella isolated from ill humans in Pennsylvania and from food animals before retail. Human clinical isolates were received from 2005 through 2011 during routine public health operations in Pennsylvania. Isolates from cattle, chickens, swine and turkeys were recovered during the same period from federally inspected slaughter and processing facilities in the northeastern United States. We found that subtyping Salmonella isolates by PFGE revealed differences in antimicrobial susceptibility patterns and, for human Salmonella, differences in sources and invasiveness that were not evident from serotyping alone. Sixteen of the 20 most common human Salmonella PFGE patterns were identified in Salmonella recovered from food animals. The most common human Salmonella PFGE pattern, Enteritidis pattern JEGX01.0004 (JEGX01.0003ARS, was associated with more cases of invasive salmonellosis than all other patterns. In food animals, this pattern was almost exclusively (99% found in Salmonella recovered from chickens and was present in poultry meat in every year of the study. Enteritidis pattern JEGX01.0004 (JEGX01.0003ARS was associated with susceptibility to all antimicrobial agents tested in 94.7% of human and 97.2% of food animal Salmonella isolates. In contrast, multidrug resistance (resistance to three or more classes of antimicrobial agents was observed in five PFGE patterns. Typhimurium patterns JPXX01.0003 (JPXX01.0003 ARS and JPXX01.0018 (JPXX01.0002 ARS, considered together, were associated with resistance to five or more classes of antimicrobial agents: ampicillin, chloramphenicol, streptomycin, sulfonamides and tetracycline (ACSSuT, in 92% of human and

  7. 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.

  8. 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

  9. Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa

    Science.gov (United States)

    Bornstein, Kristin; Hungerford, Laura; Hartley, David; Sorkin, John D.; Tapia, Milagritos D.; Sow, Samba O.; Onwuchekwa, Uma; Simon, Raphael; Tennant, Sharon M.

    2017-01-01

    Background In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis) has revealed non-typhoidal Salmonella (NTS) to be a major pathogen exhibiting high case fatality (~20%). Where infant vaccination against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged vaccines to prevent invasive NTS (iNTS) disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako. Methodology/Principal Findings A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children vaccine, were the model’s outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for use elsewhere in Africa where NTS epidemiologic patterns, serovar prevalence, and immunization schedules differ from Bamako. PMID:28182657

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Cigarette smoke and the terminal ileum: increased autophagy in murine follicle-associated epithelium and Peyer's patches.

    Science.gov (United States)

    Verschuere, Stephanie; Allais, Liesbeth; Bracke, Ken R; Lippens, Saskia; De Smet, Rebecca; Vandenabeele, Peter; Brusselle, Guy G G; Cuvelier, Claude A

    2012-03-01

    Cigarette smoke (CS) exposure is associated with increased autophagy in several cell types, such as bronchial epithelial cells. Smoking is also an environmental risk factor in Crohn's disease, in which impairment of the autophagy-mediated anti-bacterial pathway has been implicated. So far, it is unknown whether CS induces autophagy in the gut. Here, we examined the effect of chronic CS exposure on autophagy in the follicle-associated epithelium (FAE) of murine Peyer's patches. Transmission electron microscopy revealed that the proportion of cell area occupied by autophagic vesicles significantly increased in the FAE after CS exposure. An increased number of autophagic vesicles was observed in the FAE, whereas the vesicle size remained unaltered. Besides enterocytes, also M-cells contain more autophagic vesicles upon CS exposure. In addition, the mRNA level of the autophagy-related protein Atg7 in the underlying Peyer's patches is increased after CS exposure, which indicates that the autophagy-inducing effect of CS is not limited to the FAE. In conclusion, our results demonstrate that CS exposure induces autophagy in murine FAE and in the underlying immune cells of Peyer's patches, suggesting that CS exposure increases the risk for Crohn's disease by causing epithelial oxidative damage, which needs to be repaired by autophagy.

  15. Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model.

    Directory of Open Access Journals (Sweden)

    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.

  16. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis.

    Science.gov (United States)

    Malfait, A M; Gallily, R; Sumariwalla, P F; Malik, A S; Andreakos, E; Mechoulam, R; Feldmann, M

    2000-08-15

    The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA). CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete Freund's adjuvant. The CII used was either bovine or murine, resulting in classical acute CIA or in chronic relapsing CIA, respectively. CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked progression of arthritis. CBD was equally effective when administered i.p. or orally. The dose dependency showed a bell-shaped curve, with an optimal effect at 5 mg/kg per day i.p. or 25 mg/kg per day orally. Clinical improvement was associated with protection of the joints against severe damage. Ex vivo, draining lymph node cells from CBD-treated mice showed a diminished CII-specific proliferation and IFN-gamma production, as well as a decreased release of tumor necrosis factor by knee synovial cells. In vitro effects of CBD included a dose-dependent suppression of lymphocyte proliferation, both mitogen-stimulated and antigen-specific, and the blockade of the Zymosan-triggered reactive oxygen burst by peritoneal granulocytes. It also was found that CBD administration was capable of blocking the lipopolysaccharide-induced rise in serum tumor necrosis factor in C57/BL mice. Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect in CIA.

  17. Dextran sulfate sodium upregulates MAPK signaling for the uptake and subsequent intracellular survival of Brucella abortus in murine macrophages.

    Science.gov (United States)

    Reyes, Alisha Wehdnesday Bernardo; Arayan, Lauren Togonon; Simborio, Hannah Leah Tadeja; Hop, Huynh Tan; Min, WonGi; Lee, Hu Jang; Kim, Dong Hee; Chang, Hong Hee; Kim, Suk

    2016-02-01

    Brucellosis is one of the major zoonoses worldwide that inflicts important health problems in animal and human. Here, we demonstrated that dextran sulfate sodium (DSS) significantly increased adhesion of Brucella (B.) abortus in murine macrophages compared to untreated cells. Even without infection, Brucella uptake into macrophages increased and F-actin reorganization was induced compared with untreated cells. Furthermore, DSS increased the phosphorylation of MAPKs (ERK1/2 and p38α) in Brucella-infected, DSS-treated cells compared with the control cells. Lastly, DSS markedly increased the intracellular survival of Brucella abortus in macrophages by up to 48 h. These results suggest that DSS enhanced the adhesion and phagocytosis of B. abortus into murine macrophages by stimulating the MAPK signaling proteins phospho-ERK1/2 and p38α and that DSS increased the intracellular survival of B. abortus by inhibiting colocalization of Brucella-containing vacuoles (BCVs) with the late endosome marker LAMP-1. This study emphasizes the enhancement of the phagocytic and intracellular modulatory effects of DSS, which may suppress the innate immune system and contribute to prolonged Brucella survival and chronic infection.

  18. CYTOKINE PROFILE OF TH1- AND TH2-DEPENDENT VARIANTS OF CHRONIC GVHD

    Directory of Open Access Journals (Sweden)

    O. T. Kudaeva

    2012-01-01

    Full Text Available Ab