RESEARCH ARTICLE Open Access
Recu en ube culosis in Finland 1995–2013:
a clinical and epidemiological coho s udy
Vi e Ko honen
1,2,3*
, Hanna Soini
1
, Tuula Vasanka i
4,5
, Jukka Ollg en
1
, Pie e W. Smi
1,6
and Pe i Ruu u
1
Abs ac
Backg ound: We in es iga ed he epidemiology and p e alence o po en ial isk ac o s o ube culosis (TB)
ecu ence in a popula ion-based egis y coho o 8084 TB cases be ween 1995 and 2013.
Me hods: An episode o ecu en TB was de ined as a case e- egis e ed in he Na ional In ec ious Disease Regis e
a leas 360 days om he da e o he ini ial egis a ion. A eg ession model was used o es ima e isk ac o s o
ecu ence in he na ional coho . To desc ibe he p esence o known isk ac o s o ecu ence, pa ien eco ds o
he ecu en cases we e e iewed o TB diagnosis con i ma ion, po en ial ac o s a ec ing he isk o ecu ence,
he ea men egimens gi en and he ou comes o he TB episodes p eceding he ecu ence.
Resul s: TB egis y da a included 84 pa ien s, o whom mo e han 1 TB episode had been egis e ed. A e a ca e ul
clinical e iew, 50 ecu en TB cases (0.6%) we e iden i ied. The o e all incidence o ecu ence was 113 cases pe
100,000 pe son-yea s o e a median ollow up o 6.1 yea s. Fo he i s 2 yea s, he incidence o ecu ence was o e
200/100000. In mul i a ia e analysis o he na ional coho , younge age emained an independen isk ac o a all ime
poin s, and male gende and pulmona y TB a 18 yea s o ollow-up. Among he 50 ecu en cases, 35 pa ien s (70%)
had ecei ed adequa e ea men o he i s episode; in 12 cases (24%) he ea ing physician and in wo cases (4%)
he pa ien had discon inued ea men p ema u ely. In one case (2%) he ea men ou come could no be assessed.
Conclusions: In Finland, he a e o ecu en TB was low despi e no sys ema ic di ec ly obse ed he apy. The i s 2
yea s a e a TB episode had he highes isk o ecu ence. Among he ecu en cases, he obse ed p ema u e
discon inua ion o ea men in he i s episode in nea ly one ou h o he ecu en cases calls o imp o ed aining
o he physicians.
Keywo ds: Tube culosis ecu ence, Tube culosis epidemiology, Tube culosis ea men , Tube culosis
Backg ound
Tube culosis (TB) emains a majo global heal h
p oblem wi h es ima ed 10.4 million new TB cases
wo ldwide in 2015. In 2013, 0.3 million TB cases
we e epo ed as ecu en [1]. A e success ul ea -
men , ecu en TB is es ima ed o occu in 0–14% o
all TB pa ien s wi hin 1–3 yea s [2]. Recu ence o
TB ollowing ea men o an ini ial disease episode
can occu due o endogenous e-ac i a ion wi h he
same s ain o Mycobac e ium ube culosis ( elapse) o
exogenous in ec ion wi h a new s ain ( e-in ec ion).
In low-incidence coun ies, ecu ence a es ha e
a ied be ween 0.4% and in a p ospec i e clinical ial
up o 6% [3–5]. The p opo ion due o e-in ec ion
has been epo ed o a y be ween 4 and 27% [3, 4].
In high-incidence coun ies he majo i y o ecu en
cases, up o 77%, a e caused by e-in ec ion [6].
Finland is a low-TB-incidence (<10/100000) coun y
since 2001, and in 2015 TB incidence was 5/100000 [7].
In 2015, 1% o TB cases had HIV in ec ion. Howe e ,
eme ging challenges o he TB con ol p og am include
g adually inc easing esis ance o M. ube culosis, wi h
3% o all isola es mul i d ug esis an (MDR) in 2015 [7],
concomi an ly wi h a apid inc ease in he p opo ion o
TB cases occu ing in immig an s [8]. Finland did no
implemen a comp ehensi e DOT (di ec ly obse ed
he apy) s a egy in pa ien managemen un il 2013 [9].
* Co espondence: [email p o ec ed]
1
Depa men o Heal h Secu i y, Na ional Ins i u e o Heal h and Wel a e,
Helsinki, Finland
2
Depa men o Pulmona y Diseases, Tampe e Uni e si y Hospi al, Tampe e,
Finland
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Ko honen e al. BMC In ec ious Diseases (2017) 17:721
DOI 10.1186/s12879-017-2818-6
Ou p e ious s udy shows, ha in Finland mo e han
80% o ecu en cases du ing 1995–2013 we e elapses
[10]. The aim o he p esen s udy was o in es iga e in a
na ional, popula ion-based TB coho he occu ence o
ecu en TB and a ew po en ial ac o s a ec ing he isk
o ecu ence in Finland du ing he yea s 1995–2013. In
ecu en cases, we desc ibe ea men egimens adminis-
e ed and ea men ou come in he i s episode, and
o he po en ial ac o s a ec ing he isk o ecu ence, in
o de o s eng hen he TB ea men p og am in he
changing epidemiologic en i onmen .
Me hods
Su eillance sys em and s udy popula ion
The s udy popula ion consis ed o all TB cases in Finland
epo ed om Janua y 1, 1995, o Decembe 31, 2013, o
he Na ional In ec ious Disease Regis e (NIDR), main-
ained a he Na ional Ins i u e o Heal h and Wel a e
(THL). Clinical mic obiology labo a o ies manda o ily
no i y new M. ube culosis isola ions o NIDR and submi
isola es o he Mycobac e ial Re e ence Labo a o y (NRL)
a THL o d ug suscep ibili y es ing (e hambu ol,
isoniazid, py azinamide, i ampicin and s ep omycin).
Physicians manda o ily no i y o NIDR labo a o y-
con i med cases o TB: he labo a o y epo o a posi i e
es esul o he clinician au oma ically includes a
eminde o no i y he case. Since 2007, also clinically
diagnosed TB cases, when a decision o gi e a ull cou se
o TB ea men is made, a e no i ied. In o ma ion on HIV
posi i i y is ob ained by linking da a wi hin NIDR. Da a
on he coun y o o igin and he da e o dea h we e
e ie ed om he na ional popula ion egis y. Da a om
he di e en sou ces a e au oma ically linked as a case by
a unique pe son iden i ying numbe .
Case de ini ions and da a collec ion o he subg oup o
ecu en cases
An episode o ecu en TB was de ined as a case e-
egis e ed in NIDR a leas 360 days om he da e o he
ini ial egis a ion o a TB in ec ion episode. Fo he cases
who had a ecu en episode in he egis e , da a on
ana omical si e o disease (pulmona y/ex apulmona y),
adiological, his ological and mic obiological esul s, HIV
es esul s, subs ance abuse, he d ug egimen in he i s
episode and ad e se e ec s we e ex ac ed om pa ien
cha s. In pulmona y TB cases, also spu um smea and
cul u e esul s a mon hs 0 and 2, and a he end o he
ea men we e ob ained. Based on ca e ul e iew o hese
da a, a numbe o cases we e excluded om u he
analysis as ecu en cases, as hey did no mee he
c i e ia o ecu en TB (Fig. 1). In cul u e nega i e
episodes, he diagnoses we e based on clinical c i e ia
[11], including adiological indings in combina ion wi h
ei he his ological con i ma ion o posi i e nucleic acid
ampli ica ion es esul s, excep o one case in which he
diagnosis was only clinical and adiological.
Managemen o he TB episode p eceding ecu ence
The ea men egimen, ee o cha ge o he pa ien ,
adminis e ed in he i s TB episode was g ouped in o
six ca ego ies, based on he na ional ecommenda ions:
un il 2006 as desc ibed ea lie [12, 13], and om 2006 in
he Na ional TB Con ol P og am [9]. The ea men
egimens and he ou comes o he i s TB episodes o
he ecu en cases, including cul u e nega i e and ex a-
pulmona y cases, we e assessed by wo clinical TB
expe s, and classi ied [11] as cu ed, comple ed ea -
men , los o ollow-up and no e alua ed (no a al cases
no ailu es). ‘Los o ollow-up’was u he di ided in o
subg oups: physician’s decision o s op p ema u ely
(including cases ha ecei ed ine ec i e ea men ), and
de aul ed (in e up ion due o he pa ien ). G oup ‘no
e alua ed’was u he di ided in o subg oups: s ill on
ea men a 12 mon hs, and ea men ou come no
assessed. In wo cases he de ails o ea men in he i s
episode we e no a ailable, bu in one o hese cases he
ea men ou come could be assessed.
S a is ical analysis
To calcula e he incidence o ecu en TB among all
epo ed cases o he na ional coho , ollow-up ime in
days was calcula ed o all cases in he na ional TB
coho om 360 days a e hey we e no i ied un il an
e en ( e-no i ica ion), dea h o censo ed (Decembe 31,
2013). The da e o dea h was acqui ed by linkage o
popula ion egis e using pe son iden i ie . The eg es-
sion model employed, uses pseudo-obse a ions o
model censo ed da a [14] wi h S a a e sion 14.02
(S a aCo p LLC, 4905 Lakeway D i e, Collage S a ion,
TX 77845 USA) o es ima e e ec s ( hei ela i e isks)
o isk ac o s. The censo ing was assumed o be inde-
penden , condi ional on he co a ia es [15]. Gende and
ana omical si e o disease we e allowed o ha e ime
dependen e ec s, and p edic i e ma gins we e calcu-
la ed o es ima e cumula i e isk di e ences be ween
gende s and ana omical si es o disease, espec i ely,
adjus ing o o he ac o s in he model. Resul s we e
quali a i ely checked using he ex ended ime dependen
Cox model. All he explana o y a iables wi h uni a ia e
p- alues <0.2 we e included in he mul i a ia e model,
and included gende , ana omical si e o disease and age.
Cause speci ic cumula i e isks o ime poin s 1 yea ,
2 yea s and 18 yea s we e calcula ed, as he chosen ea ly
ime poin s had mos ecu en e en s o explana o y
a iables, and i has been p e iously epo ed ha he
i s 1–2 yea s ha e he highes haza d o ecu ence
[3, 16]. The maximum su eillance ime poin se a
18 yea s gi es he inal o e all di e ence es ima e o
Ko honen e al. BMC In ec ious Diseases (2017) 17:721 Page 2 o 7
he cumula i e isk o ecu ence. The dis ibu ion o
con inuous a iables be ween g oups was compa ed
using Wilcoxon ank-sum es .
E hics
The e hics app o al o he s udy was gi en by he
E hics Commi ee o Tampe e Uni e si y Hospi al,
Tampe e, Finland.
Resul s
A o al o 8084 TB cases we e egis e ed in Finland du ing
he s udy pe iod (Table 1): 43% we e emale, and 13.6% o
o eign o igin (inc eased om 4.8% in 1995 o 32.2% in
2013). The median age was 70 yea s (in e qua ile ange
[IQR], 56–79 yea s) o Finnish-bo n and 30 yea s (IQR
23–40 yea s, p< 0,001) o o eign-bo n cases.
Cha ac e is ics and incidence o ecu en TB
A e a ca e ul e iew o he 84 cases wi h mo e han one
episode egis e ed, 50 TB cases (0.6% o all cases in he
coho ) we e classi ied as ecu en (Fig. 1). The mean
o e all incidence o ecu ence was 112.9 (95% con idence
in e al [CI], 85.6–148.9); o he i s yea o ollow-up
he o e all incidence was 236.4 (95%CI 140.0–399.2) and
o he second yea o ollow-up 206.7 (95%CI 114.5–
373.2) pe 100,000 pe son-yea s. Ou o he 50 ecu en
cases, wo had h ee disease episodes and 48 wo disease
episodes. Fo y cases we e cul u e posi i e in all episodes.
The median age was 51.5 yea s ( ange 6–95 yea s) a he
egis a ion o he i s episode; ele en cases (22%) we e
emale. In he i s episode 44 cases (88%) and in he sec-
ond episode 39 cases (78%) we e classi ied as pulmona y
TB. Two cases we e HIV posi i e; o 64% o cases HIV
had no been es ed. Nine ecu en cases (18%) we e o
o eign o igin. A his o y o subs ance abuse, mos ly alco-
hol, was egis e ed in he pa ien eco ds in a leas 1 TB
episode o 59% o males and none o emales; 49% o
males had subs ance abuse eco ded in bo h episodes.
Managemen o he TB episodes p eceding ecu ence
Among he 48 ecu en cases (96%) wi h comple e pa ien
eco ds, 36 cases (75%) ecei ed s anda d ea men in he
i s episode (Table 2). Among hese, he du a ion o
Fig. 1 S eps in iden i ying ecu en cases o ube culosis, Finland, 1995–2013.
a
Non- ube culous mycobac e ium egis e ed as M. ube culosis
(N= 2), egis a ion o alse iden i y (N= 1) o inco ec egis a ion da e by he no i ie (N= 10).
b
Only one long con inuous TB episode (N= 5),
o ea ing physician decided o gi e TB ea men wi hou speci ic e idence o TB and in subsequen expe assessmen by he s udy eam he e
was ano he mo e likely cause o he disease (N=9)
Table 1 Dis ibu ion o demog aphic and po en ial isk ac o s
o ecu en ube culosis in a na ional TB coho o 8084 cases,
Finland 1995–2013
Va iable TB ecu ence
(n= 50)
No TB ecu ence
(n= 8034)
All (n= 8084)
Median age, yea s 51, 5 66 66
Gende emale n(%) 11 (22%) 3457 (43%) 3468 (42.9%)
Fo eign o igin n(%) 9 (18%) 1066 (13.6%)
a
1074 (13.6%)
b
Pulmona y si e o disease
n(%)
44 (88%)
c
5599 (69.2%) 5605 (69.3%)
Cul u e posi i e n(%) 48 (96%)
c
6631 (82.5%) 6680 (82.6%)
P io o yea 2007 n(%) 45 (90%)
c
5762 (71.7%) 5807 (71.8%)
a
O igin known o 7862 cases
b
O igin known o 7912 cases
c
Da a o he i s episode
Ko honen e al. BMC In ec ious Diseases (2017) 17:721 Page 3 o 7
ea men was sho (<5.5 mon hs) in six cases, and he in-
ensi e phase (<54 days) in h ee cases. Twel e cases (25%)
ecei ed non-s anda d ea men due o d ug esis ance,
ad e se e ec s, o he ea ing physician’s decision. O
hese, six cases ecei ed TB ea men egimens ha we e
assessed as p obably e ec i e, one o hem o a oo sho
ime pe iod. T ea men egimens o six cases we e assessed
as p obably ine ec i e. Six cases (12.5%) ecei ed di ec ly
obse ed he apy (DOT). Among he 49 cases wi h ea -
men ou come, i was success ul in 27 cases (55.1%). In 12
cases (24.5%) he ea ing physician had s opped he ea -
men p ema u ely, and in wo cases (4.1%) in e up ion was
due o he pa ien . Eigh cases (16.3%) we e s ill on ea -
men a 12 mon hs (all inally comple ed ea men ).
The e we e no ecu en cases wi h an MDR isola e in
ei he episode. Fi e cases we e ini ially in ec ed wi h
isoniazid- esis an isola es, bu in h ee o hese cases,
he ea men egimen was no modi ied acco dingly. In
wo cases, addi ional esis ance o s ep omycin and in
one case esis ance o py azinamide de eloped du ing
ea men . In one case, ini ially ully suscep ible isola e
de eloped esis ance o py azinamide.
Risk ac o s o ecu ence in he na ional coho
The median ollow-up ime o cases in he coho o
8084 TB cases was 6.1 yea s (IQR 2.7–11.1 yea s). The
ecu ence occu ed wi hin less han 2 yea s in 25 (50%),
wo o less han 4 yea s in 8 (16%), and la e in 17 cases
(34%) (Fig. 2a). No ecu ences occu ed in emales and
o ex apulmona y cases a e he i s 2 yea s (Fig. 2b
and c). In uni a ia e analysis o a iables a ailable o
he na ional coho , he cumula i e isks o ecu ence
be ween males and emales, and be ween pulmona y and
ex apulmona y TB did no di e s a is ically
signi ican ly a 1 and 2 yea s o ollow-up (Table 3).
Howe e , a 18 yea s o ollow-up, he cumula i e isk
o males was nea ly ou old compa ed o emales
(Fig. 2b), and mo e han i e old o pulmona y TB com-
pa ed o ex apulmona y TB (Fig. 2c). The isk o ecu -
ence dec eased wi h e e y addi ional 10 yea s o age
(Table 3). When only cases ha we e cul u e posi i e in
all episodes we e included, he ecu ence a e was simi-
la o ha seen in he whole ecu en cases coho
(Fig. 2d). Whe he he i s episode occu ed p io o
e sus a e 2007 did no ha e a signi ican associa ion
wi h he isk o ecu ence (Table 3).
In he mul i a ia e analysis (Table 3) younge age
emained an independen isk ac o o cumula i e isk
o ecu ence a all ime poin s, and male gende and
pulmona y TB a 18 yea s o ollow-up.
Discussion
We in es iga ed he epidemiology and he p e alence o
isk ac o s associa ed wi h ecu ence o TB in Finland
in a comp ehensi e na ional, egis e -based coho o
8084 TB cases om 1995 o 2013, and ound in a
ollow-up o up o 18 yea s ha 0.6% o cases du ing he
s udy pe iod we e ecu en . The o e all incidence o
ecu ence is 10–20 imes highe , and o he i s 2
yea s o ollow-up 20–40 imes highe han he inci-
dence o TB in he gene al popula ion in Finland du ing
he s udy pe iod [7]. Pa ien cha e iew o he ecu -
en cases e ealed ha in nea ly one ou h o he
ecu en cases, he physician had discon inued he
ea men o he i s episode p ema u ely.
In egis e -based s udies on ecu en TB, alida ion o
he da a equi es conside able e o o ensu e da a
Table 2 Dis ibu ion o ea men egimens in he i s episodes o 50 TB cases wi h a ecu ence
T ea men g oup To al in g oup In ensi e phase
sho
In ensi e phase
adequa e
Du a ion o ea men
sho
Du a ion o ea men
adequa e
S anda d ea men A
a
15 NA 15 1 14
S anda d ea men B
b
4NA4 2 2
S anda d ea men wi h sho in ensi e
phase C
c
33 NA2 1
S anda d ea men D
d
14 0 14 1 13
O he p obably e ec i e combina ion o
an i-TB d ugs
e
6NANA1 5
O he p obably ine ec i e combina ion o
an i-TB d ugs
6NANANA NA
No e alua ed 2 ––– –
NA no applicable, Hisoniazid, RRi ampicin, Zpy azinamide, Ee hambu ol
a
HRZ in in ensi e phase, HR in con inua ion phase, adequa e du a ion o ea men ≥5.5 mon hs
b
HRE in in ensi e phase, HR in con inua ion phase, adequa e du a ion o ea men ≥8 mon hs
c
Sho in ensi e phase <54 days in s anda d ea men A o B
d
≥4 an i-TB d ugs, including HRZ (adequa e du a ion o ea men ≥5.5 mon hs) o HRE (adequa e du a ion o ea men ≥8 mon hs)
e
Non-s anda d combina ions guided by d ug esis ance o due o ad e se e ec s, he adequacy o ea men du a ion assessed by he s udy g oup
D ug esis ance igno ed o inapp op ia e dosing
Re e ences [9,12,13]
Ko honen e al. BMC In ec ious Diseases (2017) 17:721 Page 4 o 7
quali y, as demons a ed in ou s udy using a egis e wi h
p o en high sensi i i y and speci ici y o TB [17], a e
which au oma ed no i ica ion om he labo a o ies and
manda o y eminde s om he labo a o y o he clinician
on he need o no i y we e in oduced. We obse ed ha
ou o he 84 cases ini ially iden i ied in he egis e da a
as ecu en , only 50 cases we e uly ecu en . Majo
easons o inaccu acies in ou egis e da a included
inco ec no i ica ion da es, and no i ying clinical TB cases
wi hou mic obiological con i ma ion, which he cha
e iew e ealed o be inco ec . Wi hou alida ion o he
da a o ecu en TB cases, he p opo ion o ecu en
a b
c d
Fig. 2 Cumula i e isk o ecu ence o TB by ollow-up ime (and i s poin wise 95% con idence limi s). aO e all coho ; (b) By gende ; (c)By
ana omical si e o disease; (d) Only cul u e posi i e TB
Table 3 Uni a ia e and mul i a ia e analysis o isk ac o s o TB ecu ence in a na ional coho o TB cases in Finland, 1995–2013
Va iables Uni a ia e RR 95% CI pMul i a ia e RR 95% CI p
Males a 1 yea
a
1,43 0,48–4,26 0,52 1,93 0,40–9,31 0,41
Males a 2 yea s
a
1,18 0,53–2,62 0,69 1,39 0,44–4,38 0,58
Males a 18 yea s
a
3,92 1,95–7,91 < 0,001 5,88 2,21–15,66 < 0,001
Pulmona y TB a 1 yea
b
1,72 0,48–6,19 0,40 4,13 0,58–29,67 0,16
Pulmona y TB a 2 yea s
b
1,87 0,70–4,99 0,21 2,00 0,43–9,33 0,38
Pulmona y TB a 18 yea s
b
5,54 2,17–14,14 < 0,001 15,15 4,98–46,08 < 0,001
Age + 10 yea s 0,87 0,77–0,98 0,03 0,83 0,70–0,99 0,04
Finnish o igin 0,64 0,31–1,33 0,23 –––
1.episode be o e 2007 1,33 0,81–2,21 0,26 –––
a
Re e ence emales. O e all p- alue o male gende in uni a ia e analysis < 0,0001 and in mul i a ia e analysis 0,0015
b
Re e ence ex apulmona y TB. O e all p- alue o pulmona y TB < 0,0001
Ko honen e al. BMC In ec ious Diseases (2017) 17:721 Page 5 o 7

cases ou o he o al coho in ou s udy would ha e been
almos double, s essing he need o igid pa ien cha
e iew when assessing TB ecu ence.
O e 80% o ecu en cases in Finland a e elapses o
he p e ious in ec ion [8], as elsewhe e in low-incidence
coun ies [3, 18, 19]. In egis e -based in es iga ions o
ecu en TB in low incidence-coun ies, ca e ul e iew
o he ac ual ea men in he i s TB pe iod o ecu -
en cases has a ely been epo ed [20, 21]. We
obse ed ha app oxima ely wo hi ds, including hose
who ecei ed ea men las ing o e 12 mon hs, had
ecei ed an adequa e ea men . Jus o e one hal
among he ecu en cases had in he i s episode a
success ul ou come acco ding o WHO c i e ia [11].
Impo an o aining policy was he inding ha clea ly
mo e equen ly han in e up ion due o he pa ien ,
he ea ing physician had discon inued ea men p e-
ma u ely, as desc ibed in ou p e ious epo [12]. Inad-
equa e ea men s we e caused by he p esence o d ug
esis ance wi hou app op ia e ea men egimen modi-
ica ion, absence o app op ia e ex ension o du a ion o
ea men when ea men was modi ied, ad e se e ec s,
o he physician’s decision o s op wi hou he eason
being documen ed in he pa ien eco d.
Theo e allincidenceo ecu encein hena ional
coho , wi h a median ollow-up pe iod o 6 yea s,
and up o 18 yea s, was 113/100000, 10–20 imes
highe han o he gene al popula ion in Finland, in
line wi h long- e m ollow-up in low-incidence coun-
ies (71–410/100000) [3, 16]. Fo he i s yea o
ollow-up, s a ing a 12 mon hs om he egis a ion
o he i s episode, he incidence o ecu ence was
236/100000, o he same magni ude as in ecen
s udies om Aus alia [3] and Denma k [18], bu
clea ly lowe han in a numbe o ea lie s udies om
indus ialised coun ies [22].
Ou obse a ion in he na ional coho o male gende
as a isk ac o o ecu ence is in line wi h some p e ious
epo s om low-incidence coun ies [23–25], bu his
inding has been inconsis en [20, 21]. Subs ance abuse
da a is no collec ed in he NIDR o he na ional coho ,
bu we ound in nea ly 60% o he ecu en male cases a
his o y o subs ance abuse in pa ien cha s, bu none in
emales, which could con ibu e o he excess isk seen in
males. An associa ion be ween ea men adhe ence and
alcoholism has been epo ed in ecu en TB in he USA
[20]. We ound in he na ional coho he isk o ecu -
ence highe o pulmona y han o ex apulmona y TB,
in line wi h ea lie s udies [16, 23, 26]. Mo e han 40% o
ou ecu en cases (da a no shown) had bo h pulmona y
and ex apulmona y in ec ion in he i s episode, which
has been epo ed o be a isk ac o o ecu ences [25].
An unexpec ed inding in he na ional coho was ha he
isk o ecu ence was associa ed wi h younge age,
whe eas in wo ea lie s udies, age > 65 yea s [20] o age
be ween 25 and 64 yea s [23] ha e been epo ed as isk
ac o s o ecu ence. In ea lie s udies, ei he being an
immig an [16, 20, 25] o being bo ne in he coun y [21]
we e epo ed as isk ac o s, while o igin was no a isk
ac o o ecu ence in ou na ional coho s udy.
Limi a ions o ou coho s udy include he ac ha we
may ail o iden i y some ecu ences, as ecu ences
be o e 360 days om he da e o he ini ial episode (ea ly
ecu ences) we e no analysed om he egis e da a. The
s anda d cu -o ime ecommended by WHO, a which
ea men ou come is eco ded, is 12 mon hs [11]. The e-
o e, we chose his imepoin as a cu -o o ecu ence,
in line wi h eg a la ge UK coho [16]. The p opo ion o
ea ly ecu ences in e ospec i e s udies is small [3, 18].
In addi ion, in e ospec i e s udies, i may be di icul o
dis inguish be ween ea men ailu es and ea ly ecu -
ences as spu um samples a e no sys ema ically collec ed
du ing ea men , and in ou s udy we also included
cul u e nega i e and ex apulmona y cases. Almos one
hi d o ou ecu en cases do no mee he WHO ea -
men egimen desc ip ion and ou come c i e ia o a
ecu en case [11]. Howe e , he ca e ul alida ion
p ocess o ou egis e da a demons a es ha he same
challenges a e likely o be p esen in o he egis e -based
s udies, unless ca e ul alida ion has been pe o med. As a
coun y wi h e y low incidence o HIV [7], he absence
o sys ema ic es ing o all TB cases o HIV is unlikely o
in oduce a bias in he isk analysis.
The obse a ions on he sho comings o ea men
among he i s episodes o he ecu en cases a e
impo an o guiding aining and sys em de elopmen
o he in eg a ed TB con ol p og am. In 2013–2015,
ea men ou come in Finland was success ul (cu e o
comple ed ea men ) in 75–78% o pulmona y TB cases
[7], as in he Eu opean Region on a e age [27].
Conclusions
In he absence o a comp ehensi e DOT s a egy, he a e
o TB ecu ence was ound o be low in Finland. An
impo an inding was ha in one ou h o he ecu en
cases, he physician had discon inued he ea men p e-
ma u ely, which implies ha aining o physicians needs
o be imp o ed and, as TB becomes a e, ea men
should possibly be p o ided in ewe cen e s. The i s 2
yea s a e a TB episode is a e y high- isk pe iod o
ecu ence: his could be inco po a ed as an au oma ed
high- isk signal in he de eloping in eg a ed elec onic
pa ien managemen sys ems o educing he delays in
implemen ing TB diagnos ics and ea men .
Abb e ia ions
CI: Con idence in e al; DOT: Di ec ly obse ed he apy; HIV: Human
immunode iciency i us; IQR: In e qua ile ange; MDR: Mul i d ug esis an ;
Ko honen e al. BMC In ec ious Diseases (2017) 17:721 Page 6 o 7
NIDR: Na ional in ec ious disease egis e ; NRL: Mycobac e ial e e ence
labo a o y; TB: Tube culosis; THL: Na ional Ins i u e o Heal h and Wel a e
Acknowledgemen s
We hank Pi jo Tu iainen, Jan-E ik Lö lund and Teemu Mö önen a he
Na ional Ins i u e o Heal h and Wel a e o echnical assis ance and
P o esso Lau i Leh imäki a he School o Medicine, Uni e si y o Tampe e
o c i ically e iewing his a icle.
Funding
The s udy was suppo ed by he Tampe e Tube culosis Founda ion, Väinö
and Laina Ki i Founda ion and The Resea ch Founda ion o he Pulmona y
Diseases. The unde s had no ole in s udy design, da a collec ion and
analysis, decision o publish, o p epa a ion o he manusc ip .
A ailabili y o da a and ma e ials
All da a gene a ed o analysed du ing his s udy a e included in his
published a icle.
Au ho s’con ibu ions
VK pa icipa ed in designing he s udy, collec ed he clinical da a, and was
in ol ed in analysing he da a and w i ing he manusc ip . HS pa icipa ed in
designing he s udy, supe ised he labo a o y wo k and was in ol ed in
analysing he da a and w i ing he manusc ip . TV pa icipa ed in designing
he s udy, and was in ol ed in analysing especially he clinical da a and
w i ing he manusc ip . JO pa icipa ed in designing he s udy and
pe o med he s a is ical analysis. PS pa icipa ed in designing he s udy and
w i ing he manusc ip . PR pa icipa ed in designing he s udy, and was
in ol ed in analysing he da a and had a majo ole in w i ing he
manusc ip . All au ho s ead and app o ed he inal manusc ip .
E hics app o al and consen o pa icipa e
The e hics app o al o he s udy was gi en by he E hics Commi ee o
Tampe e Uni e si y Hospi al, Tampe e, Finland. Consen o pa icipa e: No
applicable.
Consen o publica ion
No applicable.
Compe ing in e es s
The au ho s decla e ha hey ha e no compe ing in e es s.
Publishe ’sNo e
Sp inge Na u e emains neu al wi h ega d o ju isdic ional claims in
published maps and ins i u ional a ilia ions.
Au ho de ails
1
Depa men o Heal h Secu i y, Na ional Ins i u e o Heal h and Wel a e,
Helsinki, Finland.
2
Depa men o Pulmona y Diseases, Tampe e Uni e si y
Hospi al, Tampe e, Finland.
3
School o Medicine, Uni e si y o Tampe e,
33014 Tampe e, Finland.
4
Finnish Lung Heal h Associa ion (Filha), Helsinki,
Finland.
5
Facul y o Medicine, Uni e si y o Tu ku, Tu ku, Finland.
6
Depa men o in ec ious diseases, Public heal h labo a o y, GGD
Ams e dam, Ams e dam, The Ne he lands.
Recei ed: 13 Ap il 2017 Accep ed: 5 No embe 2017
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