Group B streptococci, a European perspective with results of the DEVANI project

In 2011, neonatal group B streptococcal (GBS) diseases remain a global public health concern. Where consensus guidelines to detect and treat intrapartum women with GBS colonization have been widely adopted, incidence of neonatal early onset disease (EOD) has dramatically declined, however despite preventive strategies cases still occur. The strategy was not expected to prevent all cases and there are challenges and limitations to this preventive approach. The best strategy for European countries is still a matter of debate and intrapartum antimicrobial prophylaxis (IAP) is not widely recommended. To adopt the best preventive strategy, we first need better data assessing more accurately the true burden of GBS diseases in the different countries. Furthermore, as the current screening-based strategy for prevention is highly effective but imperfect, given the challenges, limitations and potential complications of maternal IAP, a new approach is still needed.
Maternal immunization against GBS is an attractive alternative for the prevention of not only neonatal diseases but also stillbirths and maternal diseases. Vaccines against GBS may likely become the most effective and sustainable long-term preventive strategy. But the development of vaccines with global relevance has been hampered by changes in the distribution of GBS serotypes of strains causing diseases over time and in different parts of the world. A multivalent vaccine to cover against the more prevalent serotypes suitable for European populations might not be suitable for Asian or African populations. To overcome type-specificity, new developments target vaccines based on conserved surface antigenic proteins, such as Sip protein located at the cell surface of all GBS and on immunogenic proteins from GBS pili. A pilus-based GBS vaccine is appealing and could become a globally relevant reality.
The DEVANI (DEsign of a Vaccine Against Neonatal Infections) programme funded through the European Commission Seventh Framework was launched on 1 January 2008 with the key objective being the assessment of European GBS epidemiology to facilitate the design of a new vaccine that will confer neonatal immunity through a durable maternal immune response. A major component was to undertake pan European surveillance of maternal colonisation, maternal GBS antibody responses and neonatal diseases in eight European countries. Through 2009 and 2010, all Belgian laboratories sending any neonatal GBS invasive isolate to the National Reference Centre for GBS were invited to bring their contribution to this project.
Belgium, Bulgaria, Czech Republic, Denmark, Germany, Italy, Spain and the United Kingdom established specific GBS screening studies during 2008/10. Maternal vaginal/rectal swabs and sera were taken between 34-37 weeks gestation and processed using a standardised microbiological screening protocol. Samples from neonatal cases were processed using local procedures. For each pregnant woman and each case of GBS neonatal disease, standardized case report forms were filled. GBS isolates were characterised using standardised serological and molecular typing methods for detection of all ten GBS capsular polysaccharide types (Ia to IX). Furthermore all the collected isolates were screened by multiplex PCR and FACS analysis to evaluate respectively gene presence and surface-exposure of pili. And clonal analysis of these isolates was performed using multi-locus sequence typing (MLST).
The main microbiological results of this pan European surveillance are following. Carriage rates among pregnant women in all countries ranged from 8% to 26%. The most common GBS capsular types were III (33%), Ia (25%) and V (8%). Among GBS from EOD, the major serotypes were III (43%), V (21%) and Ia (18%). In contrast among GBS isolated from neonatal late onset disease (LOD), serotype III was highly predominant (80.6%) followed mainly by Ia (12.5%).
Analysis of the pattern of pili genes showed that all isolates contained at least one gene coding for pili. The most common gene patterns found were PI-2a alone, PI 1+2a and PI 1+2b, while the PI-2b gene alone was very rare. The most prominent result was that a majority of isolates from neonatal infections carried the PI-1+2b gene pattern, while the most common pattern among pregnant women was PI-1+2a. Most of analyzed strains express at least one pilus on their surface.
The clonal analysis showed that 66 sequence types were found to belong to nine clonal complexes (CC). Among these nine CCs, five were prevailing and covered 92 % of GBS isolates tested. The GBS population in pregnant women was found to be more heterogeneous than the GBS isolated from neonatal infection cases. Among neonatal isolates, the most frequent CC was CC17 (43 %) known as a highly virulent clone. Among participating countries, there were no significant differences in the occurrence of clonal complexes.
The analysis of the levels of specific antibodies as surrogate markers of protection is still ongoing.
More detailed and additional results as the main conclusions will be presented.