16 research outputs found

    Comparative Nationalism: Imperial Legacies and the Strength of Nationalism: The Case of China and India since the 1990s

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    Since the 1990s, there have been strong displays of nationalism in China, while in India the once dominant ‘secular’ nationalism has been challenged by a fragmentation of national identity along ethno--‐religious lines. This thesis seeks to explain why Chinese nationalism, since the 1990s, appears to be stronger and indeed more prevalent than nationalism in India. The phenomenon of nationalism in India and China has been extensively researched, yet there remains a deficiency in comparative research. Thereby, this thesis takes a historical Comparative approach through which five explanatory hypotheses are evaluated; these are entitled: direct rule, types of foreign rule, regime type, foreign threat, and diversity. The findings of this thesis suggest that China’s nationalism remains more prevalent since the 1990s, due to its experience of informal imperialism, a strong centralized Chinese state, and higher levels of militarized inter--‐state disputes. Simply, it is illustrated that because the experience of informal imperialism has centrally defined Chinese nationalism, it reacts Intensely to foreign threats that are equated to imperial acts, while the unified nature of nationalism is reinforced by a strong centralized state

    Deciphering the distance to antibiotic resistance for the pneumococcus using genome sequencing data

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    Advances in genome sequencing technologies and genome-wide association studies (GWAS) have provided unprecedented insights into the molecular basis of microbial phenotypes and enabled the identification of the underlying genetic variants in real populations. However, utilization of genome sequencing in clinical phenotyping of bacteria is challenging due to the lack of reliable and accurate approaches. Here, we report a method for predicting microbial resistance patterns using genome sequencing data. We analyzed whole genome sequences of 1,680 Streptococcus pneumoniae isolates from four independent populations using GWAS and identified probable hotspots of genetic variation which correlate with phenotypes of resistance to essential classes of antibiotics. With the premise that accumulation of putative resistance-conferring SNPs, potentially in combination with specific resistance genes, precedes full resistance, we retrogressively surveyed the hotspot loci and quantified the number of SNPs and/or genes, which if accumulated would confer full resistance to an otherwise susceptible strain. We name this approach the € distance to resistance'. It can be used to identify the creep towards complete antibiotics resistance in bacteria using genome sequencing. This approach serves as a basis for the development of future sequencing-based methods for predicting resistance profiles of bacterial strains in hospital microbiology and public health settings

    Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit

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    We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections. We investigated whether whole-genome sequencing (WGS) of MSSA surveillance would provide additional evidence for transmission. MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to WGS and bioinformatic analysis for identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. By measuring the genetic diversity in background surveillance, we defined transmission-level relatedness and identified isolates that had been unjustly assigned to clusters based on MLVA, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates provided evidence that HCWs were involved in multiple outbreaks, yet it alleviated concerns about one particular HCW. The improved resolution and accuracy of genomic outbreak analyses substantially altered the view on outbreaks, along with apposite measures. Therefore, inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference

    Diagnostic value of serum pneumococcal DNA load during invasive pneumococcal infections

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    Detection of pneumococcal DNA in blood could be a fast alternative for blood culture in invasive pneumococcal disease (IPD). In this study we compared the diagnostic value of the serum pneumococcal DNA load between different clinical syndromes in adults with bacteremic pneumococcal infections, also after initiation of antibiotic treatment. Adults hospitalized with a blood culture proven pneumococcal infection between December 2008 and June 2013 were retrospectively included. Pneumococcal DNA loads in corresponding serum samples were determined by qPCR. Data on clinical diagnosis, course of disease and antibiotic treatment were extracted from medical records. For 53 IPD cases eligible stored serum samples were retrieved. The proportion of samples positive in qPCR was lower in uncomplicated pneumonia compared with other clinical syndromes (59.5 % vs. 100 %, p = 0.005). The pneumococcal DNA load was higher in cases other than uncomplicated pneumonia (p = 0.043) as well as in more severe disease (p-values 0.018, 0.029 and 0.003 for PSI Risk Class IV/V, ICU admission and mortality, respectively). Both detection of pneumococcal DNA and distribution of load did not significantly change over the first days of hospitalization despite treatment with appropriate antibiotics. Detection of pneumococcal DNA in serum was more sensitive in clinical syndromes other than uncomplicated pneumonia. Furthermore, the pneumococcal DNA load was associated with the type of IPD and severity of disease. Since the serum pneumococcal DNA load seemed unaffected by antibiotic treatment during the first days of IPD, it may offer an alternative for culture methods after prior antibiotic use

    The role of ZmpC in the clinical manifestation of invasive pneumococcal disease

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    Item does not contain fulltextINTRODUCTION: The clinical severity and course of invasive pneumococcal disease (IPD) differs substantially between patients. Streptococcus pneumoniae harbors large genetic variability. Zinc metalloproteinase C (ZmpC), a secreted pneumococcal protein involved in neutrophil extravasation, inflammation and tissue remodeling, is present in a minority of IPD isolates. We investigated whether the presence of zmpC was associated with the clinical manifestation of IPD. MATERIAL AND METHODS: IPD patients admitted to two Dutch hospitals between 2000 and 2013 were included in the study. Detailed clinical data were collected and the serotype and presence of zmpC were determined in the corresponding blood culture isolates. RESULTS: ZmpC was present in 21% of the 542 included IPD cases and was mainly associated with serotypes 8, 4, 33A/F and 11A/D. Infection with S. pneumoniae positive for zmpC was more frequently observed in females (p=0.048) and patients with a history of smoking (p=0.033). Although no relation to clinical syndrome was observed, zmpC positive cases more often presented with cough, dyspnea and sepsis (p-values 0.026, 0.001 and 0.018), and more frequently required ICU admission (p=0.011) compared to zmpC negative cases. CONCLUSION: The presence of zmpC was associated with a more severe clinical manifestation of IPD. This study demonstrates that information on pneumococcal genetic background may be useful to identify vulnerable individuals, to monitor clinical presentation and to predict the course of IPD

    Avidity of Antibodies against Infecting Pneumococcal Serotypes Increases with Age and Severity of Disease

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    Item does not contain fulltextThe incidence of invasive pneumococcal disease (IPD) rises with age. Among adult IPD patients, the avidity of antipneumococcal polysaccharide antibodies against the infecting serotype increased with age and severity of disease, indicating that susceptibility to IPD in the elderly may rather be due to flaws in other aspects of opsonophagocytosis

    Effect of antibiotic streamlining on patient outcome in pneumococcal bacteraemia.

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    Item does not contain fulltextOBJECTIVES: In blood culture-proven pneumococcal infections, streamlining empirical therapy to monotherapy with a penicillin is preferred in order to reduce the use of broad-spectrum antibiotics. However, adherence to this international recommendation is poor, and curiously it is unclear whether antibiotic streamlining may be harmful to individual patients. We investigated whether streamlining in bacteraemic pneumococcal infections is associated with mortality. METHODS: Adults admitted to two Dutch hospitals between 2001 and 2011 with bacteraemic pneumococcal infections were retrospectively included. Detailed clinical data on patient characteristics, comorbidities and severity and outcome of disease were obtained in addition to data on antibiotic treatment. Those eligible for streamlining were selected for further analyses. RESULTS: In the 45.8% of cases (126 of 275) where antibiotic treatment was streamlined, a lower mortality rate was observed (6.3% versus 15.4%, P = 0.021). The decision to streamline was only marginally explained by the 38 determinants accounted for. After correction for potential confounders, the OR for death while streamlining was 0.45 (95% CI: 0.18-1.11, P = 0.082) in all cases and 0.35 (95% CI: 0.12-0.99, P = 0.048) specifically in pneumonia cases. CONCLUSIONS: Our results suggest that streamlining in eligible pneumococcal bacteraemia cases is safe, irrespective of patient characteristics, severity of disease or empirical treatment regimen.1 augustus 201

    Density and duration of experimental human pneumococcal carriage

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    Item does not contain fulltextThe density and duration of pneumococcal carriage are considered to affect the likelihood of transmission and invasive disease. Because of its importance in both spreading and causing disease, carriage has been suggested as an endpoint in future vaccine studies. Culture is the current gold standard for detection, but may not be sensitive enough to detect changes at low density. Healthy adult volunteers received an intranasal inoculation of Streptococcus pneumoniae serotype 6B. Pneumococcal density in nasal washes collected at six time-points post-inoculation was determined by culture and quantitative PCR (qPCR). Natural pneumococcal carriers detected at initial screening were followed in parallel. In 331 nasal washes from 79 volunteers, the sensitivity and specificity of pneumococcal detection by qPCR, as compared with culture, were 92.3% and 75.9%. The estimation of pneumococcal density by culture and qPCR was highly correlated (rs = 0.73, p <0.0001), although qPCR had a lower detection limit. Pneumococcal density fluctuated within a carriage episode, and occasionally fell below the detection limit of both methods. The duration of carriage episodes was underestimated when only one method was used. Similar fluctuations in density were observed in natural carriers. Pneumococcal carriage is a dynamic event. Culture and qPCR are complementary for surveying the density and duration of pneumococcal carriage episodes
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