New insights into the burden of severe S. pyogenes infection across Europe

Epidemiological studies can play an important role in identifying 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, paving the way for the identification of novel therapeutic targets.

A European network Strep-EURO, launched in September 2002, provided an opportunity to explore epidemiological patterns across Europe. Twelve participants across eleven countries took part in the network, funded by the Fifth Framework Programme of the EU and co-ordinated by the University of Lund in Sweden.

Diseases caused by the Lancefield group A streptococcus, Streptococcus pyogenes, are amongst the most challenging to clinicians and public health specialists alike. This common bacterium of the throat and skin causes ‘strep throat’, skin infections, scarlet fever, and severe diseases such as pneumonia, septicaemia and necrotising fasciitis. Although severe infections caused by this organism 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.

This study arose from a new collaboration between the Health Protection Agency, the National Public Health Institute in Helsinki (KTL) and the University of Helsinki, Finland.

Theresa Lamagni, of the HPA provided the epidemiological lead for the Strep-EURO network, which succeeded in collecting a wealth of data on over 5000 cases identified over two years (2003-04). Analysis of these data has 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 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 disease in injecting drug users. 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 possible 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. Analysis of additional data from the UK found use of NSAIDs (nonsteroidal anti-inflammatory drugs) to be significantly associated with development of streptococcal toxic shock syndrome (STSS), This research is providing us with valuable information surrounding the role of NSAIDs in the development of severe disease.

Several other 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.

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 UK guidance on the management of contacts, the first developed by any country in Europe.

Theresa Lamagni, one of the principal investigators for the project said,
“This is one of the most comprehensive studies of severe group A streptococcal infections ever undertaken and has provided vital information on how common these infections are in Europe, who is affected and what factors influence the risk of death.

“The research builds on our previous understanding of severe streptococcal infections and will be invaluable in the development of possible vaccines against these diseases.”