The Effect of Serotype on Early and Late Mortality in Invasive

Chloe Walsh
ACF 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 Mortality
 Traditionally 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
Serotypes
 Over 90 serotypes based on polysaccharide capsule
 “Invasive” versus “colonising”
 “Colonising” serotypes associated with poorer
outcomes
 Capsule is target for vaccination
Role of serotype
 Meta-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
Methods
 Retrospective 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)
Results
 N=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
Results
 Mortality 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
Conclusions
 IPD 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
Discussion
 Possible 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?
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