Bacterial meningitis in Finland, 1995-2014: a population-based observational study
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Polkowska A, e al. BMJ Open 2017;0:e015080. doi:10.1136/bmjopen-2016-015080
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Abs Ac
Objec i es Bac e ial meningi is emains an impo an
cause o mo bidi y and mo ali y wo ldwide. I s
epidemiological cha ac e is ics, howe e , a e changing due
o new accines and secula ends. Conjuga e accines
agains Haemophilus in luenzae ype b and S ep ococcus
pneumoniae (10- alen ) we e in oduced in 1986 and
2010 in Finland. We assessed he disease bu den and
long- e m ends o i e common causes o bac e ial
meningi is in a popula ion-based obse a ional s udy.
Me hods A case was de ined as isola ion o S.
pneumoniae, Neisse ia meningi idis, S ep ococcus
agalac iae, Lis e ia monocy ogenes o H. in luenzae om
ce eb ospinal luid and epo ed o na ional, popula ion-
based labo a o y su eillance sys em du ing 1995–2014.
We e alua ed changes in incidence a es (Poisson o
nega i e binomial eg ession), case a ali y p opo ions (χ2)
and age dis ibu ion o cases (Wilcoxon ank-sum).
Resul s Du ing 1995–2014, S. pneumoniae and N.
meningi idis accoun ed o 78% o he o al 1361 epo ed
bac e ial meningi is cases. H. in luenzae accoun ed o
4% o cases (92% o isola es we e non- ype b). Du ing
he s udy pe iod, he o e all a e o bac e ial meningi is
pe 1 00 000 pe son-yea s dec eased om 1.88 cases
in 1995 o 0.70 cases in 2014 (4% annual decline (95%
CI 3% o 5%). This was p ima ily due o a 9% annual
educ ion in a es o N. meningi idis (95% CI 7% o 10%)
and 2% dec ease in S. pneumoniae (95% CI 1% o 4%).
The median age o cases inc eased om 31 yea s in
1995–2004 o 43 yea s in 2005–2014 (p=0.0004). O e all
case a ali y p opo ion (10%) did no change om 2004 o
2009 o 2010–2014.
Conclusions Subs an ial dec eases in bac e ial meningi is
we e associa ed wi h in an conjuga e accina ion
agains pneumococcal meningi is and secula end in
meningococcal meningi is in he absence o accina ion
p og amme. Ongoing epidemiological su eillance is
needed o iden i y ends, e alua e se o ype dis ibu ion,
assess accine impac and de elop u u e accina ion
s a egies.
In oduc Ion
Despi e he a ailabili y o accines, an i-
bio ics and ad ances in in ensi e ca e,
bac e ial meningi is emains an impo an
cause o mo bidi y and mo ali y wo ldwide.
Pe sis en neu ological sequelae including
hea ing loss, neu opsychological impai -
men o seizu es a e epo ed in 10%–30%
o su i o s.1 The case a ali y p opo ion
(CFP) anges om 5% o 30% o di e en
bac e ia.2 3
Globally, S ep ococcus pneumoniae, Neis-
se ia meningi idis and Haemophilus in luenzae
a e he mos impo an causes o bac e ial
meningi is, pa icula ly in young child en.4 5
Among neona es, he mos common cause
o bac e ial meningi is is S. agalac iae,2 6
while Lis e ia monocy ogenes is impo an in
newbo ns and elde ly pe sons wi h como -
bidi ies.7 Howe e , he leading o ganisms
causing bac e ial meningi is a y by age o
he pa ien , ime and geog aphical loca ion.5
As he choice o empi ical an imic obial
ea men o bac e ial meningi is should
be based on local epidemiology, pa ien ’s
age, p esence o isk ac o s and egional
esis ance pa e ns,8–10 popula ion-based
Bac e ial meningi is in Finland, 1995–
2014: a popula ion-based
obse a ional s udy
Aleksand a Polkowska,1 Maija To opainen,2 Jukka Ollg en,2 Ou i Lyy ikäinen,2
J. Pekka Nuo i1,2
o ci e: PolkowskaA,
To opainenM, Ollg enJ, e al.
Bac e ial meningi is in Finland,
1995–2014: a popula ion-based
obse a ional s udy. BMJ Open
2017;0:e015080. doi:10.1136/
bmjopen-2016-015080
►P epublica ion his o y and
addi ional ma e ial a e a ailable.
To iew, please isi he jou nal
(h p:// dx. doi. o g/ 10. 1136/
bmjopen- 2016- 015080).
Recei ed 9 No embe 2016
Re ised 27 Ma ch 2017
Accep ed 13 Ap il 2017
1School o Heal h Sciences,
Uni e si y o Tampe e,
Lääkä inka u, Tampe e, Finland
2Depa men o In ec ious
Diseases, Na ional Ins i u e
o Heal h and Wel a e (THL),
Manne heimin ie, Helsinki,
Finland
Co espondence o
P o . J. Pekka Nuo i;
pekka. nuo i@ u a. i
Resea ch
S eng hs and limi a ions o his s udy
►This s udy desc ibes he epidemiological
cha ac e is ics o >1300 cases o bac e ial
meningi is epo ed o na ional su eillance du ing
20 yea s in Finland.
►The s udy p o ides clinically impo an in o ma ion
on he changing dis ibu ion o pa hogens and age
o cases.
►The s udy documen s he sus ained popula ion
impac o in an conjuga e accina ion agains
Haemophilus in luenzae ype b; and in oduc ion
o 10- alen pneumococcal conjuga e accina ion
on educing he bu den o bac e ial meningi is, as
well as decline in meningococcal meningi is due
o secula end. As he da a we e om labo a o y-
based su eillance sys em, clinical in o ma ion such
as se e i y o ea men was no a ailable.
►Incidence a e o bac e ial meningi is may be
unde es ima ed since cases diagnosed by PCR o
an igen de ec ion and cul u e-nega i e meningi is
cases diagnosed based on clinical symp oms and
indings we e no included in he da ase .
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su eillance da a a e impo an o help in o mula ing
clinical guidelines.
The in oduc ion o e ec i e p o ein conjuga e accines
agains H. in luenzae ype b (Hib), S. pneumoniae and N.
meningi idis has changed he epidemiology o bac e ial
meningi is in many coun ies.11 12 In Finland, uni e sal
accina ion agains Hib since 1986 esul ed in apid elim-
ina ion o he disease13 and in oduc ion o he 10- alen
pneumococcal conjuga e accine (PCV10) in Sep embe
2010 has esul ed in subs an ial educ ion in accine- ype
in asi e disease.14 15 Meningococcal conjuga e accines
(MCVs) ha e no been in oduced in o Finnish Na ional
Vaccina ion P og amme (NVP). Howe e , meningo-
coccal polysaccha ide accine has been o e ed o mili a y
consc ip s since 1982.
To p o ide in o ma ion o de eloping u u e p e en-
ion s a egies and o help in o mula ing clinical
guidelines, we conduc ed a popula ion-based obse a-
ional s udy o de e mine he con ibu ion o speci ic
pa hogens o he o al bac e ial meningi is disease
bu den and o assess long- e m ends in he incidence o
common ae iologies in Finland du ing 1995–2014.
Ma e Ials and Me hods
da a sou ces
Since 1995, all clinical mic obiology labo a o ies in
Finland ha e had legal obliga ion o epo mic obial
isola ions om blood and/o ce eb ospinal luid (CSF)
o he Na ional In ec ious Diseases Regis e (NIDR)—a
popula ion-based, elec onic labo a o y su eillance
sys em main ained by he Na ional Ins i u e o Heal h
and Wel a e (THL). Rou inely collec ed in o ma ion
include he mic obe, specimen da e, da e o bi h, sex,
place o esidence and unique Pe sonal Iden i y Code
(PIC). Fo blood o CSF indings conce ning S. pneumo-
niae, S. agalac iae, N. meningi idis, L. monocy ogenes o H.
in luenzae, mul iple no i ica ions wi h he same PIC and
mic obe a e me ged in o one case i hey occu ed wi hin
3 mon hs o he i s no i ica ion. Since 2004, in o ma ion
on i al s a us a e episode is ou inely ob ained om he
Popula ion In o ma ion Sys em. All clinical mic obiology
labo a o ies also submi isola es om epo ed cases o
THL e e ence labo a o ies o species e i ica ion and
cha ac e isa ion o he isola es including se o yping o
se og ouping. Since 2004, se o yping esul s a e linked
o NIDR no i ica ions by using he PIC. An imic obial
suscep ibili y da a we e no a ailable.
case de ini ions
We de ined a case o bac e ial meningi is as isola ion o S.
pneumoniae, S. agalac iae, N. meningi idis, L. monocy ogenes
o H. in luenzae om CSF and no i ied o NIDR om 1995
h ough 2014.
Fo cases epo ed du ing 2004–2014, we calcula ed he
pa hogen-speci ic 30-day CFP as numbe o cases esul ing
in dea h wi hin 30 days om he i s posi i e CSF cul u e,
di ided by all cases.
We calcula ed he p opo ions o S. pneumoniae, N.
meningi idis and H. in luenzae cases due o accine-p e en -
able se o ypes/se og oups du ing 2004–2014. Se o ypes
co e ed in PCV10 a e he ollowing: 1, 4, 5, 6B, 7F, 9V,
14, 18C, 19F and 23F; he 13- alen PCV13 adds se o ypes
3, 6A and 19A. Vaccine-p e en able meningococcal se o-
g oups include hose in he quad i alen MCV (MCV-4,
A, C, W and Y) and se og oup B isola es a ge ed by no el
p o ein-based accines (MenB). Fo H. in luenzae, ype b
was conside ed accine p e en able.
s a is ical analysis
By using da a om he Popula ion In o ma ion Sys em
as denomina o s, we calcula ed pa hogen-speci ic and
age-speci ic annual incidence a es. Poisson eg ession
was used o es o log-linea end in a es o bac e-
ial meningi is du ing 1995–2014. Incidence a e a ios
(IRRs), hei 95% CI and p alues o yea ly changes we e
calcula ed using ime (yea ) as a con inuous explana o y
a iable in he Poisson model. When app op ia e, we used
nega i e binomial eg ession o co ec o o e dispe -
sion o da a. To compa e age dis ibu ion o cases ac oss
yea s, we used Wilcoxon ank-sum es . To assess changes
in CFP, we used χ2 analyses; p alue <0.05 was conside ed
s a is ically signi ican . All analyses we e done wi h STATA
e sion 13 and Mic oso Excel 2013.
e hical conside a ions
Da a used in he analysis we e collec ed as a pa o
na ional ou ine su eillance which alls unde he
exis ing manda e o THL. No o mal Ins i u ional Re iew
Boa d e iew was equi ed o his s udy. Pe sonal iden i-
ie s we e emo ed a e linkage wi h i al s a us da a.
esul s
o e all incidence a es o bac e ial meningi is
F om 1995 o 2014, 1361 cases o bac e ial meningi is
caused by S. pneumoniae, N. meningi idis, S. agalac iae, L.
monocy ogenes o H. in luenzae we e epo ed (mean inci-
dence a e, 1.29 cases/100 000 pe son-yea s, able 1). S.
pneumoniae and N. meningi idis we e he mos common
ae iologies accoun ing o 78% (1061/1361) o cases. The
median age o cases inc eased om 31 yea s in 1995–2004
o 43 yea s in 2005–2014 (p=0.0004). Ra es we e highe
in men han women (1.52 s 1.07 cases/100 000 pe son-
yea s; IRR 1.4, 95% CI 1.3 o 1.6)).
The mean annual a es o all bac e ial meningi is
anged om 1.97 in 1996 o 0.70 cases/100 000 pe son-
yea s in 2014, wi h an annual dec ease o 4% (95% CI
−3% o −5%, able 1). Du ing 2004–2014, 65 pa ien s died
wi hin 30 days om cul u e (CFP, 10% (65/633)). The e
was no change in 30-day CFP om 2004–2009 (11%
(43/402) o 2010–2014 (10% (22/231), p=0.22.
cha ac e is ic o bac e ial meningi is by age g oup
Child en <2 yea s o age accoun ed o 20% o cases
(268/1361) and had he highes incidence a e (11.38
cases/100 000 pe son-yea s, able 1). The mos common
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Table 1 Numbe o cases (n), incidence a es pe 100 000 pe son-yea s (IR) and mean annual ela i e change in incidence o bac e ial meningi is, acco ding o age g oup
(yea s), Finland, 1995–2014
1995–1999 2000–2004 2005–2009 2010–2014 1995–2014 1995–2014
n IR n IR n IR n IR n IR % change* 95% CI
S ep ococcus
pneumoniae
<2 26 4.32 25 4.43 18 3.05 14 2.33 83 3.52 −4 −7 o 0
2–4 6 0.63 3 0.35 6 0.69 3 0.33 18 0.50 −1 −8 o7
5–17 13 0.31 11 0.26 7 0.17 2 0.05 33 0.20 −7 −13 o1
18–49 59 0.50 54 0.48 35 0.32 30 0.27 178 0.40 −4 −6 o 1
50–64 41 0.91 52 1.00 56 0.99 37 0.65 186 0.88 −2 −4 o 1
≥65 25 0.67 23 0.57 39 0.89 26 0.51 113 0.66 −1 −4 o 2
All age g oups 170 0.55 168 0.65 161 0.61 112 0.41 611 0.58 −2 −4 o 1
Neisse ia
meningi idis
<2 23 3.83 23 4.07 8 1.36 14 2.33 68 2.89 −4 −8 o 0
2–4 19 1.98 11 1.27 12 1.38 6 0.66 48 1.33 −6 −10 o −1
5–17 37 0.88 16 0.38 24 0.60 7 0.18 84 0.52 −8 −14 o −3
18–49 93 0.79 46 0.41 42 0.38 14 0.13 195 0.43 −10 −13 o −8
50–64 15 0.33 15 0.29 7 0.12 2 0.04 39 0.18 −12 −17 o −6
≥65 6 0.16 3 0.07 4 0.09 3 0.06 16 0.09 −7 −14 o 2
All age g oups 193 0.62 114 0.44 97 0.37 46 0.17 450 0.43 −9 −10 o −7
Haemophilus
in luenzae
<2 4 0.67 3 0.53 2 0.34 1 0.17 10 0.42 −7 −17 o 4
2–4 0 0.00 3 0.35 0 0.00 0 0.00 3 0.08 NA NA
5–17 5 0.12 4 0.10 0 0.00 2 0.05 11 0.07 −8 −17 o 3
18–49 4 0.03 2 0.02 2 0.02 6 0.05 14 0.03 5 −5 o 15
50–64 3 0.07 3 0.06 2 0.04 2 0.04 10 0.05 −3 −13 o 8
≥65 2 0.05 0 0.00 7 0.16 1 0.02 10 0.06 1 −9 o 12
All age g oups 18 0.06 15 0.06 13 0.05 12 0.04 58 0.06 −2 −7 o 2
S. agalac iae
<2 25 4.16 24 4.25 32 5.43 25 4.16 106 4.50 0 −3 o 5
2–4 1 0.10 0 0.00 0 0.00 0 0.00 1 0.03 NA NA
5–17 0 0.00 1 0.02 0 0.00 0 0.00 1 0.01 NA NA
Con inued
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1995–1999 2000–2004 2005–2009 2010–2014 1995–2014 1995–2014
n IR n IR n IR n IR n IR % change* 95% CI
18–49 2 0.02 1 0.01 1 0.01 2 0.02 6 0.01 1 −12 o 16
50–64 4 0.09 2 0.04 7 0.12 3 0.05 16 0.08 1 −9 o 8
≥65 0 0.00 7 0.17 1 0.02 3 0.06 11 0.06 −2 −11 o 9
All age g oups 32 0.10 35 0.13 41 0.15 33 0.12 141 0.13 0 −3 o 3
Lis e ia
monocy ogenes
<2 1 0.17 0 0.00 0 0.00 0 0.00 1 0.04 NA NA
2–4 0 0.00 0 0.00 0 0.00 0 0.00 0 0.00 NA NA
5–17 1 0.02 0 0.00 0 0.00 0 0.00 1 0.01 NA NA
18–49 9 0.08 3 0.03 0 0.00 3 0.03 15 0.03 −11 −19 o −3
50–64 10 0.22 3 0.06 6 0.11 4 0.07 23 0.11 −6 −13 o 1
≥65 14 0.37 13 0.32 13 0.30 21 0.42 61 0.35 0 −4 o 4
All age g oups 35 0.11 19 0.07 19 0.07 28 0.10 101 0.10 −2 −5 o 1
To al bac e ial
meningi is
<2 79 13.14 75 13.28 60 10.18 54 8.99 268 11.38 −2 −4 o 1
2–4 26 2.71 17 1.97 18 2.07 9 0.98 70 1.94 −5 −10 o 0
5–17 56 1.33 32 0.77 31 0.77 11 0.28 130 0.80 −8 −12 o −4
18–49 167 1.43 106 0.94 80 0.73 55 0.50 408 0.91 −7 −8 o −5
50–64 73 1.63 75 1.44 78 1.37 48 0.84 274 1.30 −4 −6 o −2
≥65 47 1.25 46 1.15 64 1.46 54 1.07 211 1.23 −1 −4 o 1
All age g oups 448 1.45 351 1.35 331 1.25 231 0.85 1361 1.29 −4 −3 o −5
*Mean annual ela i e change in incidence calcula ed by Poisson eg ession o nega i e binomial eg ession.
NA,no applicable.
Table 1 Con inued
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pa hogens in his age g oup we e S. agalac iae (4.50
cases/100 000 pe son-yea s) and S. pneumoniae (3.52
cases/100 000 pe son-yea s, igu e 1). F om 1995 o 2014,
he a e o bac e ial meningi is in his age g oup dec eased
by 2% annually (95% CI −4% o −1%, able 1). The a e age
30-day CFP in 2004–2014 was 2% (3/140). In child en 2–4
yea s o age, 70 cases (5%) o bac e ial meningi is we e
epo ed du ing 1995 o 2014 (1.94 cases/100 000 pe son-
yea s). The mos common pa hogens in his age g oup
we e N. meningi idis (1.33 cases/100 000 pe son-yea s)
and S. pneumoniae (0.50 cases/100 000 pe son-yea s, able
1). Du ing he s udy pe iod, he a e o all meningi is
did no change signi ican ly ( able 1). The 30-day CFP in
2004–2014 was 14% (4/128); all ou dea hs we e due o
N. meningi idis.
Child en 5–17 yea s o age accoun ed o 130 cases
(9%) o bac e ial meningi is and had he lowes a e
(0.80 cases/100 000 pe son-yea s, able 1). N. meningi idis
and S. pneumoniae we e he main causes (0.52 and 0.20
cases/100 000 pe son-yea s, espec i ely, igu e 1). F om
1995 o 2014, he a e o bac e ial meningi is dec eased
by 8% annually (95% CI −12% o −4%, able 1). The
30-day CFP was 7% (3/45); all h ee a al cases we e due
o N. meningi idis.
Adul s 18–49 yea s o age accoun ed o 408 cases
(30%) o bac e ial meningi is (0.91 cases/100 000 pe son-
yea s, able 1). N. meningi idis and S. pneumoniae caused
mos o he cases ( igu e 1), wi h incidence a es 0.43
and 0.40 cases/100 000 pe son-yea s, espec i ely. Du ing
1995–2014, he o e all a e dec eased by 7% annually
(95% CI −8% o −5%, able 1). The 30-day CFP was 8%
(13/152), wi h nine dea hs due o S. pneumoniae in ec ion.
Among pe sons 50–64 yea s o age, he e we e 274 cases
(20%) o bac e ial meningi is (1.30 cases/100 000 pe son-
yea s, able 1), o which 186 cases (68%) we e caused by
S. pneumoniae (0.88 cases/100 000 pe son-yea s, igu e 1).
Du ing he s udy pe iod, he o e all a e dec eased by 4%
annually (95% CI −6% o −2%, able 1). The 30-day CFP
was 13% (18/143), wi h mos a al cases a ibu able o S.
pneumoniae (16 dea hs).
In adul s ≥65 yea s o age, he e we e 211 cases (15%)
o bac e ial meningi is (1.23 cases/100 000 pe son-
yea s, able 1). S. pneumoniae caused 53% (113/211) o
he cases (0.66 cases/100 000 pe son-yea s), ollowed by
L. monocy ogenes. The e was no signi ican change in he
o e all a e du ing 1995–2014 ( able 1). This age g oup
had he highes 30-day CFP (19%, 24/125). Hal o he
a al cases we e due o S. pneumoniae (12 dea hs); L. mono-
cy ogenes caused 10 dea hs.
causes o bac e ial meningi is
S ep ococcus pneumoniae
F om 1995 o 2014, 611 cases o pneumococcal menin-
gi is we e epo ed. Median age was 48 yea s; 57% o
cases we e male (male o emale IRR, 1.4 95% CI 1.2
o 1.6, able 2). The o e all annual a e pe 1 00 000
pe son-yea s dec eased om 0.70 in 1995 o 0.26 in
2014 ( igu e 2), a 2% annual dec ease (95% CI −4% o
−1%, able 1).
The incidence o pneumococcal meningi is dec eased
annually by 4% (95% CI −7% o 0%), 7% (95% CI −13%
o −1%) and 4% (95% CI −6% o −1%) in age g oups
<2 yea s, 5–17 yea s and 18–49 yea s, espec i ely.
Du ing 2004–2014, S. pneumoniae accoun ed o 58%
(38/65) o a al cases (30-day CFP 12%, 38/308).
O he 308 pneumococcal meningi is cases epo ed
du ing 2004–2014, in o ma ion on se o ype was a ailable
o 296 (96%). The p opo ion o cases caused by PCV10
se o ypes dec eased om 61% (35/57) in 2004–2005 o
15% (9/36) in 2013–2014. PCV13 se o ypes accoun ed
o 70% (40/57) cases in 2004–2005 and 44% (16/36)
in 2013–2014. In child en less han 2 yea s, p opo ion
o meningi is cases caused by PCV10 se o ypes dec eased
om 75% (9/12) in 2004–2005 o 20% (1/5) in 2013–
2014. In 2014, no meningi is cases we e caused by PCV10
se o ypes.
Neisse ia meningi idis
Du ing he s udy pe iod, meningococcal meningi is
accoun ed o 450 cases (0.43 cases/100 000 pe son-yea s)
( able 1). Median age was 18 yea s and 60% o cases we e
male (male o emale IRR 1.5, 95% CI 1.3 o 1.9, able
2). The o e all annual incidence pe 1 00 000 pe son-
yea s dec eased om 0.88 in 1995 o 0.07 in 2014; he
annual dec ease was −9% (95% CI −7% o −10%, able 1).
The decline occu ed in all age-g oups excep in <2 yea s
Figu e 1 P opo ions o bac e ial meningi is cases caused by i e pa hogens acco ding o age g oup, Finland, 1995–2014.
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and ≥65 yea s o age. The incidence dec eased annually by
6% (95% CI −1% o −10%), 8% (95% CI −3% o −14%),
10% (95% CI −8% o −13%) and 12% (95% CI −8%
o −13%) in age g oups 2–4 yea s, 5–17 yea s, 18–49 yea s
and 50–64 yea s, espec i ely. The o e all 30-day CFP was
9% (14/163) and anged om 3% (1/29) among chil-
d en aged 0–1 yea s o 21% (4/19) among child en aged
2–4 yea s.
Du ing 2004–2014, in o ma ion on N. meningi idis
se og oups was a ailable o 99% o cases (161/163).
Se og oup B accoun ed o 85% (137/161) o isola es,
C 11% (17/161) and Y 4% (7/161). In child en <2 yea s,
se og oup B caused 96% (26/27) o cases. MCV-4 and
MenB accine se og oups caused 15% (24/161) and 85%
(137/161) o all cases, espec i ely.
Haemophilus in luenzae
F om 1995 o 2014, 58 cases o H. in luenzae we e epo ed
(0.06 cases/100 000 pe son-yea s, able 1). Median age
was 29 yea s and male o emale IRR was 1.0 (95% CI 0.6
o 1.7, able 2). The incidence a e anged om 0.0 cases
pe 1 00 000 pe son-yea s in 2010 o 0.25 cases in 2007
( igu e 2). Ra es in all age g oups we e s able. F om 2004
o 2014, he e we e no dea hs due o H. in luenzae.
In 2004–2014, non-encapsula ed H. in luenzae
accoun ed o 69% (18/26) , se o ype 23% (6/26) and
ype b 8% (2/26) o isola es.
S ep ococcus agalac iae
In ec ion wi h S. agalac iae accoun ed o 141 cases o
meningi is (0.13 cases/100 000 pe son-yea s), including
24 ea ly-onse cases and 78 la e-onse cases ( able 1).
The median age o cases was 30 days; male o emale IRR
was 1.03 (95% CI 0.7 o 1.4) ( able 2). Du ing he s udy
Table 2 Cha ac e is ics o bac e ial meningi is cases, Finland, 1995–2014
Cha ac e is ics S. pneumoniae N. meningi idis S. agalac iae
L.
monocy ogenes H. in luenzae To al
Gende ,
no o cases (%
o o al)
Male 347 (57) 268 (60) 70 (50) 71 (70) 28 (48) 784 (58)
Female 264 (43) 182 (40) 71 (50) 30 (30) 30 (52) 577 (42)
Age (yea s)
Median 48 18 0 68 29 36
IQR 28–62 4–35 0 56–74 6–54 5–58
Case a ali y*
No o dea hs
(no o cases) 38 (308) 14 (163) 2 (86) 11 (50) 0 (26) 65 (633)
Case a ali y
p opo ion (%) 12.3 8.6 2.3 22 0 10.3
*Da a a e o cases epo ed du ing 2004–2014.
Figu e 2 Incidence a e (pe 100 000 pe son-yea s) o bac e ial meningi is by yea and pa hogen, Finland, 1995–2014.
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Open Access
pe iod, annual a es anged om 0.06 cases/100 000
pe son-yea s in 1995 o 0.17 cases in 2014 ( igu e 2), bu
o e all a es o S. agalac iae did no change signi ican ly
(p=0.97, able 1). Du ing 2004–2014, he 30-day CFP was
2% (2/86).
Lis e ia monocy ogenes
Du ing he s udy pe iod, L. monocy ogenes caused 101 cases
o meningi is (0.13 cases/100 000 pe son-yea s), mos ly
among elde ly pe sons (median age, 68 yea s). O cases,
70% we e men (male o emale IRR 2.5, 95% CI 1.6 o
3.9, able 2). O e all incidence a es o Lis e ia meningi is
did no a y signi ican ly du ing he s udy pe iod, anging
om 0.04 o 0.21/100 000 pe son-yea s ( able 1). The
o e all 30-day CFP was 22% (11/50) and 28% (10/36) in
pe sons ≥65 yea s o age.
dIscussIon
Du ing 1995–2014, he mos common causes o bac e ial
meningi is in Finland we e S. pneumoniae and N. meningi -
idis. Howe e , con ibu ion o speci ic pa hogens o he
disease bu den a ied subs an ially by age. As in o he
de eloped coun ies, S. agalac iae was he mos common
cause o bac e ial meningi is in child en <1 yea s o age.6
The mean age o cases inc eased signi ican ly du ing
he s udy pe iod mainly because o he dec ease in inci-
dence in child en associa ed wi h PCV10 p og amme and
declining secula end in meningococcal meningi is.
Du ing he s udy pe iod, signi ican declines we e seen
in o e all incidence o bac e ial meningi is—p ima ily
due o dec eases in a es o N. meningi is and S. pneu-
moniae. O in e es , he dec ease in incidence o N.
meningi idis was g ea e han o pneumococcal menin-
gi is, al hough he e is no ou ine accina ion p og amme
o meningococcal disease in Finland. Changes in a es o
meningococcal disease ha e also been obse ed in o he
coun ies in Eu ope and wo ldwide.16 17 The easons
o hese declines in incidence a e no clea bu may be
ela ed o popula ion immuni y o ci cula ing s ains,
changes in colonising o ganisms in he nasopha ynx
o inc easing use o in luenza accine. Also, changes
in beha iou al isk ac o s such as lowe p e alence
o smoking o c owding migh con ibu e.18 19 In some
coun ies, dec eases we e ela ed o meningococcal acci-
na ion. A e he in oduc ion o conjuga e se og oup C
meningococcal accine, accine se og oup disease nea ly
disappea ed in England20 and he Ne he lands.21 Di ec
and indi ec (he d p o ec ion) accine e ec s we e also
epo ed om o he Eu opean coun ies including
Spain, I eland and Belgium.22 23 Immunisa ion o high
isk g oups wi h ecen ly licensed p o ein-based accines
a ge ed agains meningococcal se og oup B migh also
be conside ed in Finland. Howe e , upda ed cos -e ec i e
analysis is needed o decision-making abou in oduc-
ion o meningococcal accina ion p og ams.
Be o e he in oduc ion o PCV10, conside able a i-
a ion in pneumococcal meningi is incidence a es was
seen. As he e we e no majo changes in su eillance
o diagnos ic p ac ices in Finland, hese changes may
be ela ed o eme gence o new se o ypes, selec i e
p essu e om an ibio ic use o na u al luc ua ion in
se o ypes.24–26 The decline in pneumococcal meningi is
incidence in child en <2 yea s o age was associa ed wi h
in oduc ion o PCV10 in he NVP in 201015; PCV10 se o-
ypes in his age g oup we e signi ican ly educed and by
2014 no accine se o ype meningi is cases we e epo ed.
In accine-eligible child en, he o e all a e o pneumo-
coccal meningi is was educed by 46% as a esul o a
69% educ ion in PCV10- ype meningi is.15 Many s udies
in USA and Eu ope ha e also documen ed signi ican
declines in he incidence o pneumococcal meningi is in
bo h accina ed and un accina ed g oups a e in oduc-
ion o PCV p og ammes.11 12 27–29 In Finland, i migh be
possible o achie e u he educ ions wi h highe alency
conjuga e accine o mula ions.
The incidence a e o L. monocy ogenes, N. meningi idis
and S. pneumoniae was highe in men han women. L.
monocy ogenes meningi is cases we e 2.5 imes mo e likely
o be men. Highe a es o lis e iosis in males ha e also
been obse ed in o he s udies.7 Howe e , he easons
a e unknown, bu may be ela ed o highe p e alence o
unde lying condi ions, alcoholism among men and li e
diseases (including alcoholic ci hosis).30 In pneumo-
coccal and meningococcal meningi is, possible easons
may be highe p e alence o unde lying medical condi-
ions,smoking and alcoholism.31 As lis e iosis is p ima ily
ansmi ed h ough con amina ed ood, impo an
p e en ion e o s include heal h educa ion abou die a y
guidelines o high isk g oups, such as p egnan women
and he elde ly.32
The o e all 30-day CFP o meningi is did no change
signi ican ly du ing 1995–2014. Howe e , he unchanged
CFP may be ela ed o he al e ed age dis ibu ion o
cases. Olde age is associa ed wi h highe isk o poo
ou come.33 In addi ion, pa hogen dis ibu ion has
changed and he case a ali y o meningococcal menin-
gi is is lowe compa ed wi h pneumococcal meningi is.
The small numbe o a al cases in ou s udy did no allow
assessing changes in CFP by age g oup and pa hogen. The
30-day CFP was highes o L. monocy ogenes (22%), which
is compa able wi h esul s om he Ne he lands and
Spain.7 34 Mos o he a al cases o bac e ial meningi is in
pe sons ≥50 yea s we e a ibu able o S. pneumoniae. Cases
who had pneumococcal meningi is we e olde han hose
who we e in ec ed wi h o he encapsula ed bac e ia and
likely had highe p e alence o como bidi ies inc easing
he isk o pneumococcal in ec ion and poo ou come.35
Because o lack o clinical da a, we could no assess he
po en ial impac o ea men changes, such as dexa-
me hasone use, on case a ali y. The ela i ely high CFP
emphasises he impo ance o immedia e ini ia ion o
ea men and suppo i e ca e a e diagnosis o imp o e
ou come o bac e ial meningi is.
As expec ed, H. in luenzae was he leas common cause o
bac e ial meningi is. Howe e , he s able numbe o cases
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8Polkowska A, e al. BMJ Open 2017;0:e015080. doi:10.1136/bmjopen-2016-015080
Open Access
o e 20 yea s sugges exis ence o small g oup o indi id-
uals wi h isk ac o s o H. in luenzae (such as ch onic
espi a o y disease and impai ed immuni y).36 Conju-
ga e accina ion has nea ly elimina ed Hib meningi is in
many high-income coun ies.37 38 Howe e , changes in he
epidemiology o in asi e H. in luenzae ha e been obse ed
and cu en ly mos cases occu in adul s39 and non-encap-
sula ed, non- ypable H. in luenzae ha e domina ed since
2004.
Because he da a on labo a o y con i med cases a e
ansmi ed elec onically di ec ly om he clinical mic o-
biology labo a o ies’ da abase o he na ional su eillance
da abase, a s eng h o ou s udy is comp ehensi e case
asce ainmen . In addi ion, almos all isola es o N.
meningi idis, H. in luenzae and S. pneumoniae (98%) we e
a ailable o se o yping/g ouping a THL e e ence
labo a o y. Howe e , ou s udy has se e al limi a ions. As
he da a we e om labo a o y-based su eillance sys em,
in o ma ion on clinical p esen a ion o ea men was no
a ailable. The e o e, cul u e-nega i e meningi is cases
diagnosed on he basis o clinical symp oms and indings
we e no included in he analysis da ase . In addi ion,
cases diagnosed by PCR o an igen de ec ion we e no
included. As CSF cul u es a e nega i e in 11%–30% o
pa ien s wi h bac e ial meningi is,40 he o al numbe o
meningi is cases is unde es ima ed. Ano he limi a ion is
ha NIDR da abase does no include in o ma ion on he
cause o dea h. Howe e , mos o dea hs associa ed wi h
bac e ial meningi is occu ea ly (wi hin 14 days o admis-
sion), sugges ing ha hey we e ela ed o he in ec ion.41
In conclusion, his s udy desc ibes he epidemiolog-
ical cha ac e is ics o >1300 cases o bac e ial meningi is
epo ed o na ional su eillance o e 20 yea s. I docu-
men s he sus ained popula ion impac o in an conjuga e
accina ion agains Hib and in oduc ion o PCV on
educing bu den o bac e ial meningi is as well as decline
in meningococcal meningi is due o secula end.
Howe e , disease bu den had shi ed o olde people and
no changes in he o e all p opo ion o a al cases we e
seen. Da a on changes in causa i e o ganisms and age
dis ibu ion o meningi is cases a e impo an o e al-
ua ing clinical guidelines o empi ical an ibio ic he apy
in bac e ial meningi is. Con inued epidemiological
su eillance is necessa y o moni o changing ends and
se o ype dis ibu ion, assessing he impac o accina ion
p og ams and de eloping u u e accina ion s a egies.
Con ibu o s S udy concep and design: AP, OL, PN. Acquisi ion o da a: MT, JO,
OL, PN. Analysis and in e p e a ion o da a: AP, MT, JO, OL, PN. D a ing o he
manusc ip : AP, PN. C i ical e ision o he manusc ip o impo an in ellec ual
con en : AP, MT, JO, OL, PN. S a is ical analysis: AP, JO. Ob ained unding: PN. S udy
supe ision: PN. Final app o al: AP, MT, JO, OL, PN.
Funding This s udy was suppo ed by he School o Heal h Sciences, Uni e si y o
Tampe e and he Na ional Ins i u e o Heal h and Wel a e (THL) in Helsinki, Finland.
Compe ing in e es s None decla ed.
E hics app o al Da a used in he analysis we e collec ed as a pa o su eillance
and in ec ion con ol ac i i ies which alls unde he exis ing manda e o he Na ional
Ins i u e o Heal h and Wel a e (THL).
P o enance and pee e iew No commissioned; ex e nally pee e iewed.
Da a sha ing s a emen No addi ional da a a e a ailable.
Open Access This is an Open Access a icle dis ibu ed in acco dance wi h he
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pe mi s o he s o dis ibu e, emix, adap , build upon his wo k non-comme cially,
and license hei de i a i e wo ks on di e en e ms, p o ided he o iginal wo k is
p ope ly ci ed and he use is non-comme cial. See: h p:// c ea i ecommons. o g/
licenses/ by- nc/ 4.0/
© A icle au ho (s) (o hei employe (s) unless o he wise s a ed in he ex o he
a icle) 2017. All igh s ese ed. No comme cial use is pe mi ed unless o he wise
exp essly g an ed.
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