The epidemiology of severe Streptococcus pyogenes disease in Europe

Diseases caused by the Lancefield group A streptococcus, Streptococcus pyogenes, are amongst the most challenging to clinicians and public health specialists alike. Although severe infections caused by S. pyogenes are relatively uncommon, affecting around 3 per 100,000 of the population per annum in developed countries, the case fatality is high relative to many other infections. Despite a long scientific tradition of studying their occurrence and characteristics, many aspects of their epidemiology remain poorly understood, and potential control measures undefined. Epidemiological studies can play an important role in identifying host, pathogen and environmental factors associated with risk of disease, manifestation of particular syndromes or poor survival. This can be of value in targeting prevention activities, as well directing further basic research, potentially paving the way for the identification of novel therapeutic targets. The formation of a European network, Strep-EURO, provided an opportunity to explore epidemiological patterns across Europe. Funded by the Fifth Framework Programme of the European Commission s Directorate-General for Research (QLK2.CT.2002.01398), the Strep-EURO network was launched in September 2002. Twelve participants across eleven countries took part, led by the University of Lund in Sweden. Cases were defined as patients with S. pyogenes isolated from a normally sterile site, or non-sterile site in combination with clinical signs of streptococcal toxic shock syndrome (STSS). All participating countries undertook prospective enhanced surveillance between 1st January 2003 and 31st December 2004 to identify cases diagnosed during this period. A standardised surveillance dataset was defined, comprising demographic, clinical and risk factor information collected through a questionnaire. Isolates were collected by the national reference laboratories and characterised according to their M protein using conventional serological and emm gene typing. Descriptive statistics and multivariable analyses were undertaken to compare characteristics of cases between countries and identify factors associated with increased risk of death or development of STSS. Crude and age-adjusted rates of infection were calculated for each country where a catchment population could be defined. The project succeeded in establishing the first European surveillance network for severe S. pyogenes infections, with 5522 cases identified over the two years. Analysis of data gathered in the eleven countries yielded important new information on the epidemiology of severe S. pyogenes infections in Europe during the 2000s. Comprehensive epidemiological data on these infections were obtained for the first time from France, Greece and Romania. Incidence estimates identified a general north-south gradient, from high to low. Remarkably similar age-standardised rates were observed among the three Nordic participants, between 2.2 and 2.3 per 100,000 population. Rates in the UK were higher still, 2.9/100,000, elevated by an upsurge in drug injectors. Rates from these northern countries were reasonably close to those observed in the USA and Australia during this period. In contrast, rates of reports in the more central and southern countries (Czech Republic, Romania, Cyprus and Italy) were substantially lower, 0.3 to 1.5 per 100,000 population, a likely reflection of poorer uptake of microbiological diagnostic methods within these countries. Analysis of project data brought some new insights into risk factors for severe S. pyogenes infection, especially the importance of injecting drug users in the UK, with infections in this group fundamentally reshaping the epidemiology of these infections during this period. Several novel findings arose through this work, including the high degree of congruence in seasonal patterns between countries and the seasonal changes in case fatality rates. Elderly patients, those with compromised immune systems, those who developed STSS and those infected with an emm/M78, emm/M5, emm/M3 or emm/M1 were found to be most likely to die as a result of their infection, whereas those diagnosed with cellulitis, septic arthritis, puerperal sepsis or with non-focal infection were associated with low risk of death, as were infections occurring during October. Analysis of augmented data from the UK found use of NSAIDs to be significantly associated with development of STSS, adding further fuel to the debate surrounding the role of NSAIDs in the development of severe disease. As a largely community-acquired infection, occurring sporadically and diffusely throughout the population, opportunities for control of severe infections caused by S. pyogenes remain limited, primarily involving contact chemoprophylaxis where clusters arise. Analysis of UK Strep-EURO data were used to quantify the risk to household contacts of cases, forming the basis of national guidance on the management of infection. Vaccines currently under development could offer a more effective control programme in future. Surveillance of invasive infections caused by S. pyogenes is of considerable public health importance as a means of identifying long and short-term trends in incidence, allowing the need for, or impact of, public health measures to be evaluated. As a dynamic pathogen co-existing among a dynamic population, new opportunities for exploitation of its human host are likely to arise periodically, and as such continued monitoring remains essential.

EU Accession and FDI inflows : The cases of the Czech Republic and Slovakia

Central and East European countries have faced a difficult process of transition since the dissolution of the Soviet bloc. Ten transition countries (Hungary, Poland, teh Czech Republic, Slovakia, Slovenia, Lithuania, Latvia, Estonia, Bulgaria and Romania have chosen to join the EU and have moulded their transition reforms to ensure the compliance of their legal and institutional framework with EU requirements. The high levels of FDI attracted by the candidate countries for EU membership had been attributed to rapid transition of the countries aiming to join the European Union and the fact that favourable evaluations by EU authorities of the progress made by the candidates had a large impact on improving investor confidence. The aim of this paper is to investigate the reform strategies of the Czech Republic and Slovakia undertaken when the countries were preparing for EU membership and the dynamics of FDI inflows into these economies. Subsequently a comparative analysis of FDI stocks in these countries is conducted. We find that both countries faced similar economic challenges in implementing structural and institutional reforms. In accordance with EU requirements the Czech Republic and Slovakia have perfected their legal and institutional framework, increased the authority of regulatory and supervisory bodies and focused on implementation of new or amended legislation. During the period of the analysis (1998 - 2007) the Czech Republic and Slovakia have attracted increasing amounts of FDI. Comparative analysis in terms of important determinants of FDI reveals further similar features: macroeconomic stability; an open and liberalised market; low labour costs compared to EU-15 and a similar breakdown of FDI inflows by investor country. Consequently, the fact that the Czech Republic received much larger volumes of net FDI inflows could be attributed to the difference in market size between the two states. This conclusion is consistent with previous empirical studies that list market size among the main determinants of FDI. However, when we look at FDI as a percentage of GDP the evidence is more mixed. In 2004 - 2007, Slovakia has surpassed the Czech Republic twice. Whether this tendency will persist remains to be seen. The analysis in this paper based on empirical data. However, the choice of the method, namely case studies and comparative analysis, means that the conclusions of this study are theoretical and remain to be further tested in quantitative models.