Invasive pneumococcal disease

Despite the large number of serogroups and serotypes known, most cases of invasive pneumococcal disease (IPD) on a global scale are attributed to the 1, 3, 4, 6, 7, 9, 14, 18, 23 (Jefferson, 2006) and 19a serogroups.

Risk of complications

Invasive pneumococcal infection can manifest as meningitis, bacteraemic pneumonia, bacteraemia without a focus, and bacteraemia with a focus other than the lungs or meninges (e.g. endocarditis, osteomyelitis, and arthritis, although rare). Complications, such as pneumonia or otitis media, are also possible with non-invasive forms of infection but are not considered in this study.

Most observed complications of invasive bacterial diseases, including IPD, are related to the meningitis event. The risk of meningitis was estimated using surveillance data reported to TESSy on clinical presentations of the acute symptomatic disease (ECDC, 2013) and it was found that 10% of IPD cases are reported to manifest meningitis. The risk of developing meningitis during the acute phase of the disease is age-specific. Age and gender-specific data were extracted from ECDC’s TESSy database on the risk of developing meningitis for IPD cases from 2010 to 2011 (see Table 4). The risk of developing long-term sequelae is age and gender-specific.

Long-term sequelae

Bacterial meningitis may cause long-term sequelae and permanent disabilities. In order to account for these, information was extracted on the risk of developing permanent sequelae from Edmond et al. (Edmond, 2010).

Meningitis can result in various long-term sequelae: cognitive difficulties (4.2%), seizure disorders (2.5%), hearing loss (7.5%), motor deficit (5.8%), visual disturbance (1.1%), behavioural problems (4.6%) multiple (5.7%) and clinical impairments (3.3%) (Edmond, 2010). Therefore, we assumed that 10% of all IPD patients would be at risk of developing long-term sequelae.

Case fatality proportion

The case fatality proportion for invasive pneumococcal disease has been estimated at 18% in a population-based study of 19 000 people (Harboe, 2009); however, important differences were observed between age groups, with a lower (3%) mortality rate observed in children <5 years. The overall lethality rate due to bacteraemia is about 10–20% (CDC, 2009; Rudan, 2009; Lin, 2010; Saldías, 2009) and may be as high as 60% among elderly patients (CDC, 2009).

Overall mortality due to endocarditis is 50%, but it can reach 60–65% in children (Elward, 1990). The case-fatality proportion for pneumococcal meningitis is about 30%, but may be as high as 80% in elderly persons (CDC, 2009; Burckhardt et al. 2010). The parameters for the case fatality proportion were based on data for EU/EEA countries in 2011, see Table 3 (ECDC, 2013).

Model input summary

Table 1. Transition probabilities used in the outcome tree

Health outcome
(Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Hearing loss

 

0.75%

Edmond, 2010

Cognitive difficulties

 

0.42%

Edmond, 2010

Seizure disorder

 

0.25%

Edmond, 2010

Motor deficit

 

0.58%

Edmond, 2010

Visual disturbance

 

0.11%

Edmond, 2010

Behavioural problems

 

0.46%

Edmond, 2010

Clinical impairments

 

0.33%

Edmond, 2010

Multiple impairments

 

0.57%

Edmond, 2010

Fatal cases  due to symptomatic infection

 

See Table 3

(3-24%)

Harboe, 2009

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Symptomatic infection

0.655 (0.579-0.727)

Intensive care unit admission

0.027-0.038

Tunkel, 2004
Assuming the duration of antimicrobial therapy

Permanent disability following meningitis

 

 

Remaining life expectancy

 

1. Hearing loss

0.008-0.103

From lowest to highest hearing loss related DWs

 

 

2. Cognitive difficulties

0.044-0.188

From lowest to highest intellectual disability related DWs

 

 

3. Seizure disorder

0.07 (0.057-0.088)

Generic uncomplicated disease: worry and daily medication

 

 

4. Motor deficit

0.011-0.421

From lowest to highest motor impairment related DWs

 

 

5. Visual disturbance

0.004-0.171

From lowest to highest vision impairment related DWs

 

 

6. Behavioural problems

0.088 (0.07-0.108)

Subacute sclerosing panencephalitis – phase 1 (assuming best fitting health state description)

 

 

7. Clinical impairments

0.004-0.421

From lowest to highest DW included in this model

 

 

8. Multiple impairments

0.004-0.421

From lowest to highest DW included in this model

 

 

Table 3. CFP following symptomatic infection

Age

 CFR

0

5.1%

1-4

3%

5-14

7.1%

15-64

8%

≥65

14.3%

Table 4. Age specific distribution per gender of the 60-63% risk of developing meningitis manifestation during the symptomatic infection (TESSy 2010-2011)

Age
group

%

F

M

0

10.37

11.45

01-04

8.13

8.52

05-09

2.70

3.56

10-14

1.54

2.54

15-19

0.39

1.57

20-24

1.29

1.22

25-29

1.02

2.23

30-34

2.45

3.56

35-39

3.29

5.68

40-44

3.74

5.58

45-49

5.47

6.90

50-54

6.70

7.31

55-59

9.21

7.76

60-64

11.28

9.02

65-69

9.78

7.04

70-74

7.60

6.24

75-79

6.51

4.91

80-84

5.15

2.98

85+

3.36

1.93

Total

100

100

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