Pneumococcal disease

Streptococcus pneumoniae (the pneumococcus) is the leading vaccine preventable cause of pneumonia, septicaemia and meningitis and is estimated to be responsible for about 15 million cases of disease and over 800,000 deaths in young children in the year 2000 (O’Brien 2009).

[CDC]

Pneumococcal disease is both treatable, through administration of antibiotics, and preventable, by vaccination, but both of these strategies are compromised by the extraordinary adaptability of this genetically diverse pathogen. The frequency of detection of multidrug resistant pneumococci has steadily increased since the 1970’s, but it is notable that resistant isolates tend to be members of a small number of genotypic lineages, some of which have been seen to spread around the globe (McGee 2001).

The recent deployment of conjugate pneumococcal vaccines (PCV) targeting the bacterial capsular polysaccharides of the lineages most associated with disease has led to vaccine evasion due to the processes of serotype replacement and capsular switching made possible by the enormous existing pneumococcal strain diversity.

Implementation of strategies to control pneumococcal disease are proceeding without a detailed understanding of how the pneumococcus evolves in response to these clinical interventions, or the ability to precisely monitor emerging evolutionary patterns in the circulating global pneumococcal population.

It is a well established reality that acquisition of antibiotic resistance occurs in most pathogen species, but the mechanisms by which these adaptations are occuring is only partially understood and the extent to which different mechanisms contribute to changes in the population have barely been sampled.

Understanding these evolutionary changes and monitoring their dynamics in evolving pneumococcal lineages would provide the ability to measure the response of this pathogen to vaccine evasion by selection of resistance and allow for further interventions to be designed.


The pathogen – Streptococcus pneumoniae

[wikipedia]
Somewhat paradoxically, Streptococcus pneumoniae (the pneumococcus) is one of the leading causes of death due to bacterial infection worldwide yet it is most commonly found as a harmless resident of the human nasopharynx.

Carriage rates vary between global regions with higher rates in resource-poor countries where the disease burden is also higher. Infant carriage rates in these countries can be as high as 95% while in resource-rich countries rates of around 20% are more typical.

The pneumococcus has been studied in detail for decades – it is the organism which Avery and colleagues used in the 1940’s to confirm DNA as the “transforming principle” – and several genetic loci have been studied as candidate virulence determinants. However the distinction between harmless carriage and devastating disease remains mysterious with little information to distinguish carriage isolates from disease isolates.


Mapping the Pneumococcal Genome