A public health and budget impact analysis of vaccinating at-risk adults and the elderly against pneumococcal diseases in Germany

Figures & data

Figure 1. Modeling approach: simulating vaccination over time.

PCV13: 13-valent pneumococcal conjugate vaccine; PPV23: 23-valent pneumococcal polysaccharide vaccine.

Figure 2. Model structure: disease progression simulation.

IPD: Invasive pneumococcal disease.

Figure 3. Observed and modeled sero-epidemiological changes of the incidence of pneumococcal serotypes causing invasive pneumococcal disease over time from 2005 to 2021.

IPD: Invasive pneumococcal disease; PCV7: Seven-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPV23: 23-valent pneumococcal polysaccharide vaccine.Data taken from [13,31].

Figure 4. Net difference in outcomes (number of invasive pneumococcal disease cases) over 5 years if the 13-valent pneumococcal conjugate vaccine replaces 23-valent pneumococcal polysaccharide vaccine.

Scenario A assumed comparable vaccine effectiveness between 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine. Scenario D assumed very high vaccine effectiveness for 13-valent pneumococcal conjugate vaccine and very low vaccine effectiveness for 23-valent pneumococcal polysaccharide vaccine. Negative numbers indicate net decrease in the number of cases while positive numbers indicate net increase.IPD: Invasive pneumococcal disease.

Figure 5. Net budget impact (strategy with vs without 13-valent pneumococcal conjugate vaccine by scenario and recommendation.

PCV13: 13-valent pneumococcal conjugate vaccine.

Table 1. Scenario analysis (accounting for the uncertainties of parameters).

Parameter		Scenario A		Scenario B		Scenario C		Scenario D
		PPV23	PCV13	PPV23	PCV13	PPV23	PCV13	PPV23	PCV13
Vaccine effectiveness (serotype-specific) (%)	Against IPD, E and AR i.c.	74 [15]	74	50	60	80	90	50	90
	Against IPD, E and AR i.s.	35 [16]	35	1	1	69	69	1	69
	Against NBPP, E and AR i.c.	39 [49]	39	0	0	64	64	0	64
Disease-related costs (%)				-20		+20		-20
Change in IPD incidence in adults over time	PCV7 [36,39]	Decrease		Decrease		Decrease		Decrease
	PCV13 not PCV7	Decrease		No change		Decrease		No change
	Not PCV13 [36,39]	Increase		No change		Increase		No change

AR: At-risk adults; E: The elderly; IPD: Invasive pneumococcal disease; i.c.: Immunocompetent; i.s.: Immunosuppressed; PCV7: Seven-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPV23: 23-valent pneumococcal polysaccharide vaccine.

Table 2. Model parameters: vaccine effectiveness.

Parameter	Base-case value	Ref.
Vaccine effectiveness against IPD (scenario A; %)	E and AR i.c.: 74	[15,16]
	E and AR i.s.: 35
Vaccine effectiveness against NBPP (scenario A; %)	E and AR i.c.: 39	[49]
	E and AR i.s.: 0
Waning function of vaccine effectiveness (%)	Year 1: 82	[50,51]
	Year 2: 78
	Year 3: 72
	Year 4: 64
	Year 5: 54
	Year 6: 43
	Year 7: 30
	Year 8: 15
	Year 9: 0
	Year 10: 0
Time to receive revaccination	5 years	[48]
Proportion of the vaccinated receiving revaccination	3%, only for those who received the initial vaccination below 60 years old	[31]

AR: At-risk adults; E: The elderly; IPD: Invasive pneumococcal disease; i.c.: Immunocompetent; i.s.: Immunosuppressed; NBPP: Nonbacteremic pneumococcal pneumonia.

Table 3. Model parameters: costs.

Parameter	Base-case value	Ref.
PPV23 vaccine (per dose)	€30.25	[109]
PCV13 vaccine (per dose)	€65.02	[109]
Administration of vaccine	€6.95	[31]
Meningitis	€11,664	[54]
Invasive pneumonia	€8075	[54]
NBPP: inpatient	€5762	[54]
NBPP: outpatient	€78	[54]
Proportion of NBPP patients hospitalized (by age band in years; %)	5–55: 7.8	[54]
	56–64: 16.6
	65+: 34.5
Post-meningitis sequelae: hearing loss (per year)	€1552	[55]
Post-meningitis sequelae: other neurological sequelae (per year)	€862	[54,55,110]

NBPP: Nonbacteremic pneumococcal pneumonia; PCV13: 13-valent pneumococcal conjugate vaccine; PPV23: 23-valent pneumococcal polysaccharide vaccine.

Table 4. Model parameters: clinical parameters.

Parameter	Base-case value (range used in the univariate sensitivity analysis)	Ref.
Split by risk group (%)	AR i.c.: 12.82 (12.81–12.82)	[57]
	AR i.s.: 0.25 (0.2–0.3; as a proportion of the size of nonelderly adult population)
Incidence of IPD in 2005 (per 100,000 person-years) by age band in years (%)	16–44: 2.5	[5]
	45–64: 8.5
	65–74: 24.1
	75+: 10.3
Risk of developing IPD	AR i.c.: 5.494	[56,57]
	AR i.s.: 35.833 (compared with the nonelderly adult population)
IPD incidence by serotype in 2005 (%)	PCV7: 45.7	[13]
	PCV13: 76.3
	6A: 3.1
	PPV23: 89.4
	Others: 7.7
Herd protection effect: decrease in incidence of IPD associated with PCV serotypes^†	Cumulative gamma distribution	[36,39]
	α: 0.5061
	β: 3.0406
Serotype replacement effect: increase in incidence of IPD associated with non-PCV serotypes^†	Cumulative gamma distribution	[36,39]
	α: 1.4086
	β: 7.6955
Incidence of nonbacteremic pneumonia (per 100,000 person-years) by age group in years (%)	18–19: 33.0	[60]
	20–29: 44.0
	30–39: 63.0
	40–49: 77.0
	50–59: 134.0
	60–69: 298.0
	70–79: 739.0
	80–89: 1762.0
	90+: 3581.0
Proportion of nonbacteremic pneumonia having pneumococcal origin (%)	40	[61]
Proportion of meningitis in IPD (%)	8.2	[31]
Proportion of meningitispatients with post-meningitis sequelae (%)	52 (22% with hearing loss and 30% with other neurological sequelae)	[62]
Case–fatality rate: meningitis (by age band in years; %)	5–49: 21	[58]
	50–64: 21
	65+: 39
Case–fatality rate: invasive pneumonia (by age band in years; %)	5–49: 1	[58]
	50–64: 9
	65+: 20
Relative risk of dying from IPD by serotype (%)	PCV13: 95.3	[59]
	PPV23 not PCV13/6A: 113.2
	Not PPV23/6A: 112.7
Case–fatality rate: NBPP (%)	8.6	[61]

^†As a function of cumulative pneumococcal conjugate vaccine coverage in children.

AR: At-risk adults; IPD: Invasive pneumococcal disease; i.c.: Immunocompetent; i.s.: Immunosuppressed; NBPP: Nonbacteremic pneumococcal pneumonia; PCV7: Seven-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPV23: 23-valent pneumococcal polysaccharide vaccine.

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