Chloe WalshACF infectious diseases

MSc by thesis (part time)Supervisors: Dr Gavin Barlow, Dr Victoria Allgar

What is Invasive Pneumococcal Disease?

Pneumococcus is a gram positive bacterium that colonises the upper respiratory tract.

Can become pathogenic

Invasive Pneumococcal disease (IPD) is diagnosed when Pneumococcus is isolated from a normally sterile site.

Why is IPD important?Around 2 million deaths are attributed to

Pneumococcus globally per annum

Local study of IPD (Elston et al) found that 21.6% of patients died within 30 days of diagnosis

36.8% of patients died within one year of diagnosis.

Overall incidence of IPD of 11.8/100000 in 2002, increasing to 16.4/100000 by 2009

IPD and MortalityTraditionally considered an acute illness

Both pneumonia and sepsis have been associated with longer term mortality

Determinants of this poorer long term outcome are not fully understood

SerotypesOver 90 serotypes based on polysaccharide

capsule

“Invasive” versus “colonising”

“Colonising” serotypes associated with poorer outcomes

Capsule is target for vaccination

Role of serotypeMeta-analysis has shown 1, 7F and 8 to be

associated with better outcomes (“low severity”)

3, 6A, 6B, 9N and 19F are (“high severity”)

Although relationship to acute deaths has been studied, whether serotypes influence longer term mortality has not been established

MethodsRetrospective cohort

All patients admitted to Hull Royal Infirmary or Castle Hill with IPD between 2002 and 2009 identified

Serotype recorded where available and classified as “low severity”, “high severity” or “other”

Demographic data also collected (sex, age at time of sample and index of multiple deprivation (IMD) score)

ResultsN=553

Mean age 59.4

46% female

Mean IMD 31.9 (range 1.6-81.5)

Overall mortality at 30 days, 1 year and 2 years respectively 22.9%, 36.9% and 42.4% respectively

ResultsMortality in patients with lower risk

serotypes (1, 7F and 8) (n=123) was lower than with higher risk serotypes (3, 6a, 6B, 9N and 19F) (n=75); 11.4% versus 21.3% at 30 days (p =0.012).

At 1 and 2 years p<0.001

Increasing age (p<0.001) and male sex (p=0.003) also associated with increased mortality at 2 years.

Mortality rate at 30 days, 1 year and 2 years by Serotype Group

Cumulative survival by Serotype Group

ConclusionsIPD is associated with increased mortality

up to 2 years following infection

Infection with a “high severity” serotype is associated with worse outcome

No evidence that infection with “low severity” serotype is associated with increased long term mortality

DiscussionPossible that patients who have infections

caused by “high severity” serotypes have a lower barrier to infection due to underlying co-morbid illness

Ongoing work to further establish factors associated with poor long term outcomes

Important to understand the role of serotype for future vaccine development

Thank you,

Questions?