Meeting on review of core consensus methods for s. pneumoniae carriage
29-30 March 2012, Geneva, Switzerland
Pneumococcus is a major cause of worldwide mortality and morbidity that is vaccine-preventable. New pneumococcal conjugate vaccines are expected to be licensed in the coming years, and protein-based and non-capsular vaccines are under clinical testing. Carriage of pneumococcus precedes disease and is the reservoir for spread between people. Understanding the impact of vaccine on carriage would advance decision-making for both new and existing pneumococcal vaccines.
Carriage of SPn may be used to assess the likely effectiveness and impact of pneumococcal conjugate vaccines (PCV). The factors implicated in the precise assessment of carriage and carriage serotypes are still inadequately understood. Researchers argue that studies that estimate invasiveness on the basis of the ability of pneumococcal strains to progress from nasopharyngeal (NP) carriage to invasive disease are in part subjective. Carriage studies undertaken up to now have used conventional microbiological techniques to identify the dominant serotype carried by a given child.
In 1998, The World Health Organization established a Working Group of experts to establish core, standardized methods for the study of pneumococcal NP colonization that could be used in the PCV studies. The use of standardized methods has helped to facilitate comparisons of results between studies without the confounding effect caused by differences in study methodology. The Core Consensus Methods have provided a common methodology to conduct pneumococcal NP colonization studies with reduced inter study method variability.
However, these carriage methods are not optimal for the assessment of pneumococcal carriage as they do not permit the detection of multiple serotypes or the quantification of carriage. In addition improvements in the areas of transport and storage of samples need to be reviewed. Moreover, originally these methods were designed for use in the context of clinical trials. However, in recent years following the introduction of PCV vaccines, it has become clear that shifts in the SPn population biology and subsequent serotype replacement is the dominant threat to PCV use. Thus, the focus of carriage studies is moving from evaluation of vaccine efficacy to monitoring of serotype replacement following introduction.
In addition, following the work of the PneumoCarr consortium, it has become more accepted that assessment of impact on carriage is a useful component of the regulatory process, offering regulators an additional parameter against which to assess new or improved vaccines. Standardization and improvement of the methods for measuring SPn carriage will be essential both for the regulatory process and post introduction evaluation. Lastly, ongoing discussions suggest that future vaccines could be licensed using data on their impact on nasopharyngeal carriage and not on immunological correlates of protection. The question remains if reduction in nasopharyngeal carriage and/or transmission would be sufficient for licensure, along with pneumonia efficacy data.
- The aim of this meeting was to update the current WHO-approved methods (O'Brien et al, PIDJ 2003). A discussion paper was circulated prior to the meeting, covering such areas as specimen collection and transport, identification and serotyping, to facilitate robust discussion leading to development of new consensus guidelines.
- A report on updated consensus methods published in an IVB document and an article in a peer review paper.