High caseload of childhood tuberculosis in hospitals on Java Island, Indonesia: a cross sectional study.
2 .0 0
Re se arch ar t icle
H igh ca se loa d of ch ildh ood tu be rcu losis in h ospita ls on Ja va I sla n d, I n don e sia : a cross
se ction a l stu dy
T risasi Lest a ri 1 * , Ari Pr o b an d ar i 2 , An n a- Ka rin Hu r t ig 3 an d Ad i Ut a rin i 1
* Corresp on din g aut hor: Trisasi Lest ari t risasilest ari@g m ail.com
1
Depart m en t of Public Healt h, Facult y of Medicine Univ ersit as Gad j ah Mada, ( Jl Farm ak o, Sek ip Ut ara) , Yogy akart a, ( 5 528 1) , I ndonesia
2
Depart m en t of Public Healt h, Facult y of Medicine Univ ersit as Sebelas Maret , ( Jl. I r. Su t am i 36A) , Surak art a, ( 57 126 ) , I n donesia
3
Depart m en t of Public Healt h and Clin ical Medicine, Um eå Univ ersit y, Um eå, ( SE- 9 01 8 5) , Sw ed en
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Abstr a ct
Ba ck g rou n d
Childhood t uberculosis ( TB) has been neglect ed in t he fig ht ag ainst TB. Despit e im p lem ent at ion of Direct ly Observ ed Treat m ent Short course
( DOTS) p rogram in pub lic and priv at e hospit als in I nd on esia since 200 0, t he burden of childh ood TB in hospit als was largely unk nown . Th e g oals of
t h is st udy were t o docum ent t he caseload and t y pes of ch ild hood TB in t he 0- 4 an d 5- 1 4 y ear age grou ps diag nosed in DOTS h osp it als on Java
I sland , I nd on esia.
M e t h od s
Cross- sect ional st udy of TB cases record ed in inpat ient an d out pat ien t regist ers of 3 2 hospit als. Cases w ere an alyzed b y h osp it al charact erist ics,
ag e g roup s, an d t yp es of TB. Th e n um b er of cases rep ort ed in t he out pat ien t u nit was com pared wit h t hat record ed in t he TB regist er.
Re su lt s
Of 5 ,877 TB cases in t he in pat ien t u nit and 1 5,69 4 in t h e out pat ient unit , 1 1% ( 6 48) an d 27 % ( 4,1 73) respect iv ely w ere children . Most of t he
childhood TB cases were u nder fiv e y ears old ( 56% and 53% in t he inp at ient and out pat ient clin ics resp ect iv ely ) . The prop ort ion of sm ear posit iv e
TB w as t wice as high in t he inp at ient com pared t o t he ou t p at ient un it s ( 15 .6% v s 8.1% ) . Ex t ra- pu lm onary TB accou nt ed for 15 % an d 6% of TB
cases in inp at ient and out pat ient clin ics resp ect iv ely. Am on g children recorded in hospit als only 1.6 % were rep ort ed t o t he Nat ional TB Program .
Con clu sion
I n response t o t he hig h caseload and gross u nder- rep ort ing of ch ild hood TB cases, t h e Nat ion al TB Prog ram sh ou ld g iv e h igh er priorit y for childhood
TB case m anagem ent in d esignat ed DOTS hospit als. I n ad dit ion, an int ernat ional gu idan ce on childh ood TB recordin g and report in g and im proved
diagn ost ics and st and ardized classificat ion is required
Ba ck groun d
Childhood t uberculosis ( TB) has been neglect ed in t he glob al effort s t o con t rol TB, [ 1,2 ] because it is consid ered t o b e rarely cont ag ious and
difficult t o d iagnose. I t is difficult t o con firm on bact eriological ex am in at ion of spu t u m , not ab ly if only m icroscopy is availab le [ 3,4 ] .
Th e WHO est im at ed t hat 11% of all n ew TB cases diagn osed in 20 00 w ere children [ 5] . Th e p roport ion is higher in h igh TB- burden coun t ries,
reflect ing t h at childh ood TB rep resent s act iv e TB t ran sm ission wit hin a com m un it y. A recent t uberculin surv ey est im at ed t hat 3.2% t o 6.8% of all
children in Cent ral Java Prov ince hav e TB in fect ion [ 6] . The proport ions est im at ed for low- an d m iddle- incom e count ries rang e from 15 % t o 4 0 % of
all TB cases, wh ile it accou nt ed on ly for 0.2 % t o 6% of not ified n ew sput um sm ear posit iv e ( SS+ ) cases from 22 h igh burden coun t ries [ 5 ,7] .
Howev er, t h e n um b er of not ified childh ood TB cases m ay not reflect t h e t rue burden of childh ood TB because of t he in ad eq uacy of exist ing
surveillance syst em s and p oorly docum ent ed dat a [ 8] . The WHO guidelin es h av e already requ est ed count ries t o rep ort child TB dat a in t w o age
grou ps ( 0 - 4 and 5- 1 4 y ears old) , h ow ev er, v ery few cou nt ries com p ly [ 9] .
Sim ilar t o ot her hig h bu rd en cou nt ries, I ndonesia faces ch allenges in cap t u ring ch ild hood TB cases t o be t reat ed u nder t h e Nat ion al TB Prog ram
( NTP) . Before t he int rod uct ion of a scoring chart as a st andardized app roach t o t he d iag nosis of childhood TB in 2 007 , t h e d iagnosis of childh ood TB
was based on chest X- ray and/ or TB sign s an d sy m pt om s. The scorin g chart com p rises h ist ory of cont act w it h a sm ear spu t u m posit iv e case,
posit iv e t ub erculin sk in t est ( TST) , weigh t , fev er, cou gh, lym ph enlargem ent , bone an d j oin t enlargem ent s, and su ggest iv e ch est X- ray [ 10 ] .
Howev er, t h e sensit ivit y and sp ecificit y of t he I n donesian scoring ch art have not been validat ed and t h e cost for TST t est is st ill h igh an d only
av ailable at hospit als and ch est clinics.
Despit e im plem ent at ion of Direct ly Observed Treat m en t Sh ort - course ( DOTS) st rat eg y in hospit als since 200 0 [ 1 1] , t he bu rd en of ch ild hood TB in
t h ese hospit als w as largely un kn ow n. The goals of t his st u dy were t o d ocu m ent t h e caseload an d t yp es of childh ood TB in t h e 0 - 4 and 5- 1 4 y ear
ag e g roup s diagn osed in DOTS hospit als on Jav a I sland , I nd on esia.
M e t h ods
Th is is a cross- sect ional st ud y t hat was part of a larger research on assessm ent of t he im plem ent at ion of DOTS st rat egy in h osp it als in Jav a I sland ,
I nd on esia. The st udy was condu ct ed from 1 Au gust 20 06 t o 31 May 20 07 in all six p rov inces of Java t o collect TB dat a from cases diag nosed in
200 5 t o ensu re t hat all pat ien t s h ad com plet ed t h eir t reat m ent .
I n 2 005 , a t ot al of 15 3 ( 3 1% ) h osp it als on Java I slan d were t rained in DOTS st rat egy by t he NTP an d t he hospit als were d esignat ed as DOTS
hospit als. One hun dred an d one DOTS hospit als were select ed t h roug h qu ot a sam pling an d st rat ified based on bed capacit y ( large an d sm all) ,
ow nersh ip ( pub lic and priv at e) , and t each ing funct ion ( t eachin g and n on - t eaching) . Th ree hospit als declined t o p art icip at e for adm inist rat iv e
reason s. I nclusion crit eria for a su b- st ud y on caseload of ch ild hood TB w ere t h e av ai labilit y of a st and ardized hospit al m orbid it y report in inp at ient
an d out pat ien t u nit s, and a TB regist er for t he year 2 005 . On ly 32 h osp it als m et t hese inclusion crit eria and were select ed for t h e st ud y. These
hospit al charat erist ics, i.e. bed capacit y, ownership an d t eaching fu nct ion were n ot sig nifican t ly d ifferent from t h e h osp it al populat ion ( p 0.1 , 0.1
and 0.4 respectively, α = 5%).
A half- d ay m eet ing w as cond uct ed in each province t o exp lain t he st udy 's p urpose and prot ocol. On e represent at ive from each h osp it al was
ap point ed as t h e cont act p erson resp on sible for con firm in g t he av ailabilit y of d at a n eed ed . A t rained research assist an t w as t hen sent t o each
hospit al for t hree d ay s t o collect TB dat a in 200 5.
Th e research assisst an t s collect ed dat a on: ( 1) Hospit al p rofiles ( hospit al size, own ership an d t eaching st at u s) , wh ich w ere collect ed from a
self- adm inist ered q uest ion naire; ( 2) Dat a on TB cases am ong ad ult s and ch ild ren w ere ob t ain ed from t he hospit al m orbidit y report for t h e inpat ient
( RL2A) an d t he ou t p at ient un it ( RL2B) an d ( 3 ) Dat a on TB cases regist ered in t he DOTS program ( TB 03) .
RL2A and RL2 B are t h e n at ional st andardized form s cont ainin g t he ag greg at ed dat a report in g hospit al m orbidit y, w hich are grou ped based on t he
I nt ern at ional Code of Disease version 10 ( I CD- 1 0) . I n t hese report s, TB is coded un der I CD- 10 A1 5.0 - A19.0 , an d classified furt h er in t o nine grou p
of d iseases, i.e. sm ear sp ut um p osit ive TB ( A15 .0) , ot her p ulm on ary TB ( A15.1 - A16 .2) , respirat ory t ract TB ( A16 .3- 9 ) , m eningit is TB ( A17.0 ) ,
ot her cen t ral nervous sy st em TB ( A17.1 - A17 .9) , b on e and j oint TB ( A18.0 ) , ly m p haden it is TB ( A1 8.2) , m iliary TB ( A19 ) and ot her TB ( A1 8.1,
A18.3 , A18.8 ) . Wit h in t he 'ot her p ulm on ary TB' grou p in t h e RL2 A an d RL2B form s ( A1 5. 1- A16.2 ) , bact eriologically, h ist olog ically, or cult u re
con firm ed TB cases ( A1 5.1 t o A15.9 ) were com b ined w it h un con firm ed TB cases ( A1 6.1 t o A16.2 ) . Therefore, it was not possible t o calculat e all
con firm ed TB cases from t h e h osp it al m orb idit y rep ort . We t reat ed t his grou p as uncon firm ed cases because t h e cu rrent pract ice in diagn osing
childhood TB in I ndonesia rarely used bact eriologically, h ist olog ically or cu lt ure confirm at ion. To sim plify ou r analy sis, w e fu rt her com bin ed 'ot h er
pulm onary TB' ( A1 5.1 - A16.2 ) and ' ot her respirat ory TB' ( A16 .3 - A1 6.9) grou ps in t o 'u nconfirm ed p ulm on ary TB" ( A15 .1 - A1 6.9) . We also
com bin ed differen t g roup s of ex t ra- pu lm onary TB ( A1 7.0, A1 7.1 - A17.9 , A18.1 - 3, A1 8.8 , and A19.0 ) in t o one grou p of 'EPTB' ( A1 7.0 - A19.0 ) .
Th erefore, we have t hree groups of disease classificat ion in t h is st udy, i.e. t u bercu losis of lun g, confirm ed b y sp ut um m icroscopy wit h or wit h ou t
cult ure ( A15 .0) , u nconfirm ed p ulm on ary TB ( A15.1 - A16 .9) , and ex t ra- p ulm on ary TB ( A1 7.0 - A19 .0) . Due t o t he nat ure of t he ag greg at e dat a
sou rces, it was not possible t o verify t h e d iagnost ic m et hods in ind iv idu al cases and t o con firm t he diagn osis of TB.
I n I ndonesia, hospit als are m ainly classified accordin g t o t he nu m ber of b ed s av ailab le, own ership, and t each ing cap acit y. Large and sm all, pu blic
an d priv at e, or t each ing an d non- t eachin g hospit al feat u re un iqu e com p lexit ies in t he im p lem ent at ion of DOTS program . Th e ch i- sq uare t est and
t w o- prop ort ion z- t est w ere used t o calcu lat e differences bet w een g roup s of ch ild hood TB in different t y pes of hospit als, t yp es of TB, an d age grou ps
accordin g t o t he WHO recom m end at ion ( i.e. 0- 4 an d 5- 14 y ear- old ) . The find ing s are su m m arized separat ely for in pat ien t s and ou t p at ient s. We
div id ed t h e n um b er of childhood TB cases in t h e TB reg ist er by t he t ot al num ber of ch ildh ood TB cases recorded in t he hospit al m orbid it y report in
t h e inpat ient an d out pat ien t u nit t o obt ain t he proport ion of childh ood TB t reat ed u n der t h e DOTS st rat egy. St at ist ical an alyses were carried ou t
usin g Ep i I n fo soft ware v ersion 3 .3.2 and Microsoft Ex cel.
Et hical app rov al was ob t ain ed from t he Et hics Com m it t ee, Facult y of Med icin e, Un iv ersit as Gadj ah Mad a. Perm ission t o con duct t he st u dy was
receiv ed from each hospit al.
Re su lt
Un d e rre p ort in g of ch ild h ood TB t re a t e d u n d e r t h e D OTS st ra t e g y
I n 2 005 , a t ot al of 4,8 21 ch ild ren ( 648 in t he in pat ien t u nit and 4 ,173 in t he out pat ien t u nit s) w ere diagn osed as TB pat ien t s in 32 hospit als on
Java I slan d. How ev er, t here was a larg e d iscrep an cy b et ween t he num ber of childh ood TB cases b eing d iagnosed in t h e h osp it al an d t hose t hat
were act u ally report ed t o t h e NTP. Out of 3 2 hospit als, only 1 1 hospit als recorded ch ild hood TB in t heir TB regist ry ( TB0 3 form ) . Overall, only 75 ou t
of 4 ,821 ( 1.6 % ) childh ood TB cases in hospit als w ere act ually recorded in t he TB regist ers and report ed t o t h e NTP. The m aj orit y of cases report ed
were 5 t o 14 y ears old ( 75% ) an d classified as p ulm on ary cases ( 6 5% ) . Sp ut um sm ear ex am in at ion w as carried ou t in 39 cases ( 5 2% ) , and 9
( 23 % ) were p osit ive. Only one case receiv ed child friend ly an t i TB form ulat ions, and t h e rest received a st an dard ad ult reg im en.
Prop ort ion of ch ild h ood TB ca se s a m on g a ll TB ca se s
Children con st it u t ed 1 1% and 2 7% of all TB cases in t h e inpat ient an d out pat ien t u nit s, resp ect iv ely. Tab le 1 shows t he caseload of childh ood TB by
hospit al t yp e. I n in pat ien t u nit s, t he prop ort ion of childhood TB was sign ificant ly h igher in larger an d t eaching h osp it als ( p < 0.01 ) , bu t d id n ot
differ sign ificant ly by hospit al own ership. I n con t rast , am ong ou t p at ient un it s, t h e p roport ion of ch ild hood TB w as significant ly larg er ( p < 0.0 1) in
sm all and non- t each ing hospit als, as well as in pub lic h osp it als.
T ab le 1 . Caseload of ch ild hood TB in different t y pes of hospit als
Table 2 d escrib es caseload an d t yp es of childh ood TB based on age grou ps in t h e inpat ient an d out pat ien t u nit s. The m aj orit y of ch ild hood TB cases
in t he in pat ien t u nit were ch ild ren aged 0 - 4 y ears ( 5 6% ) . I n reg ards t o TB t y pes, m ost w ere classified as un con firm ed pu lm onary TB ( 6 9% ) . The
prop ort ion of t h ose wit h sput um sm ear or cu lt ure p osit ive TB an d EPTB was eq ual, i.e. 16 % an d 15 % . Children wit h sp ut um sm ear posit iv e TB
con t rib ut ed up t o 5% of all spu t u m sm ear p osit ive TB cases t reat ed in t he inp at ient u n it an d 20 % of t hese children ( 20 ou t of 10 1 cases) were less
t h an fiv e y ears old. There w ere no differen ces in t he dist ribu t ion of EPTB bet ween ag e g roup s ( p = 0.08 ) .
T ab le 2 . Typ es and prop ort ion of childhood TB in inpat ient an d out pat ien t u nit
Th e findings also showed t hat t h e p roport ion of ch ild hood TB cases und er fiv e years old in t he out pat ien t u nit s was slight ly higher t h an in t he
inp at ient un it s ( 53 % in out pat ient unit s, 5 6% in inp at ient un it s) . I n som e g en eral hospit als, t he nu m ber of out pat ient childhood TB cases
surpassed t h e n um b er of ad ult TB cases ( d at a not sh ow n) . The m aj orit y of cases were classified as 'un con firm ed pu lm onary TB' ( 86% ) , followed by
sput um sm ear posit iv e TB ( 8% ) and EPTB ( 6% ) . The proport ion of children wit h sput um sm ear posit iv e TB out of all spu t u m sm ear p osit ive TB
cases t reat ed at t h e out pat ient unit w as 1 6% , t hree t im es higher t h an it s prop ort ion in t h e inpat ient unit and m ore t han half ( 52% ) were below five
years of age.
Table 3 d escrib es t y pes of EPTB in t h ree m aj or groups accord ing t o I CD 10 classificat ion, i. e. TB of t he nervous sy st em ( A17 , 36% ) , TB of ot h er
organs ( A18, 5 2% ) and m iliary TB ( A19 , 11.2 % ) . Tu bercu losis of t h e n erv ou s syst em in t h e inpat ient an d out pat ien t u nit was dom inat ed b y
m enin git is TB ( 9 5% , dat a n ot shown ) and occurred eq ually at d ifferent age grou ps. Tu b ercu losis periph eral ly m p hadenopat h y w as t he m ost
com m on t yp e of TB of ot her organs ( 6 4% ) and m ost ly occurred am on g older children . Mil iary TB was pred om inant am ong y oung children ( 68 % ) .
T ab le 3 . Typ es of ext ra- pulm onary t uberculosis
Discu ssion
Ou r st ud y ident ified t wo m ain find ing s: first ly, t he high p roport ion of ch ild ren d iag nosed wit h TB in all t y pes of h osp it als t h roug hout Java islan d;
an d secon dly, gross u nder report ing of childh ood TB cases t reat ed in t he DOTS desig nat ed h osp it al t o t he NTP.
A key find ing report ed in t his st ud y is t h e fact t h at only 11 ou t of 32 t rained h osp it als im p lem ent ing t h e DOTS st rat egy record ed childhood cases in
t h e st andardized TB reg ist er and report ed t hem t o t he NTP. Th e t ot al n um b er of regist ered childhood TB cases was only 1.6 % of all childhood TB
cases t reat ed in hospit als, indicat in g a poor disease surveillance syst em for ch ild hood TB in t he cou nt ry. Th is ph en om en on is not unique t o
I nd on esia, as weak su rv eillan ce d at a for childh ood TB in m any ot her cou nt ries is com m on du e t o difficult y in d iagnosis, and as a resu lt , lim it ed
childhood TB ep idem iolog ical st udies h av e been con duct ed. Ev en in a w ell- resou rced coun t ry such as in t h e UK, an est im at ed 20% of all ch ild hood
TB cases in 2 004 were not report ed t o t h e TB surv eillance sy st em [ 12] . I n Sout h Africa, only 56 % of m en ing it is TB cases were report ed t o t he NTP
[ 13 ] . This sit u at ion reflect s t he perceived low priorit y of childhood TB in g en eral, and w eak int ern al lin kage wit h pediat ric unit s in t he
im p lem ent at ion of t he DOTS st rat egy in hospit als.
Con seq uent ly, NTP is unlik ely t o accu rat ely capt ure t h e b urden of childhood TB, im p ai ring accurat e plan nin g and m an ag em en t , inclu din g logist ics,
i.e. t h e su pply of child- frien dly ant i TB drugs in DOTS hospit als. The fact t hat on ly on e report ed case received ant i TB drug s from t he NTP m ay
illust rat e t he lim it ed use of child- friend ly an t i TB d ru gs in hospit als, and t herefor e n on - st an dard ized TB drug form ulat ions are cont in uously
prescrib ed .
Th e p roport ion of ch ild hood TB in t he ou t p at ient un it was t en t im es h igh er t han t he est im at ed proport ion of all t y pes of ch ild hood TB for t h e
I nd on esian populat ion ( 27% v s 2.7 % ) . This finding, h ow ev er, corresponds w ell wit h t h e est im at ed childhood TB caseload in low and m idd le- in com e
cou nt ries, w hich rang ed from 1 5% t o 4 0% of all TB cases [ 7 ] . I n Java I slan d, hospit als rem ain t o be t h e first healt h provider of choice. Half of
households w it h previou s TB h ist ory survey ed in t he Nat ional TB Prev alen ce Su rv ey 2 00 4 chose h osp it als for TB t reat m ent [ 1 4] . Furt her analy sis of
childhood TB caseloads in differen t h osp it al charact erist ics su ggest t h at bu rd en of p ublic hospit als w ere hig her com p ared t o p rivat e h osp it als. Cases
referred t o h osp it al also t end t o be m ore severe com p ared t o ot her h ealt h facilit ies, such as prim ary healt h care. Th erefore it is m ore lik ely t o det ect
TB cases in h osp it al. Hence, our result cann ot be ext rap olat ed t o t he general populat ion d ue t o pot en t ial select ion b ias.
Con sist en t w it h fin din gs from ot her st u dies,[ 1 5- 1 9] m ore t h an half of childhood TB cases occurred in t he ag e g roup of 0 - 4 y ears ( i.e. 5 6% in t h e
inp at ient and 5 3% in t h e out pat ient unit ) . High incid en ce of TB am on g children un der five y ears of age in dicat es ong oing d isease t ransm ission in
t h e h ou seh old [ 2 0] . This can be prev ent ed wit h t he provision of I soniazid Prophy lax is Therapy ( I PT) in approxim at ely 60 % of at - risk ind iv idu als
[ 21 ] . Accord ing t o t he WHO recom m endat ion, I PT should be giv en for six m on t h s t o children aged less t han fiv e years w ho are household cont act s
of infect iou s cases [ 9 ,22] . I n I ndonesia, howev er, con t act t racing an d provision of TB p roph ylax is t o hig h- risk children are st ill rarely im plem en t ed.
Con t rary t o t he usu al op inion , t h e p roblem of ch ild hood TB also poses a serious pu bli c healt h issue du e t o a h igh prop ort ion of SS+ TB seen in
children in t his st u dy. These cases are as infect ious as sput um sm ear posit iv e ad ult TB cases and t hey can be t h e source of infect ion s for ot h er
children [ 20 ] . The WHO est im at ed t h at t he prop ort ion of children wit h sp ut um sm ear posit iv e TB am ong all not ified spu t u m sm ear p osit ive TB
cases for I ndonesia ran ged from 0.2% t o 4.8% , w it h an est im at ed p roport ion of 1 .1% [ 5 ] . I n ou r st ud y, t he prop ort ion in hospit als was higher, u p t o
5% in t h e inpat ient unit and 16% in t he ou t p at ient un it . Th e p roport ion of sm ear posit iv e cases am on g childh ood TB cases report ed t o t he NTP was
ev en higher ( 23 % or 9 out of 39 ch ild hood TB cases wit h sm ear sput um result ) . Anot h er st udy in hig h endem ic set t ing s fou nd a proport ion of 5.8 %
of all childhood TB were sm ear p osit ive in t h e Kilim an j aro region [ 15 ] , 5% in Malawi,[ 19 ] 4.7 % in I ndia [ 23] , an d 20 % in Thailan d [ 2 4] . This
find ing challeng es a com m on p ercept ion t hat y oung children wit h TB are rarely con t agi ou s [ 25 ] . Hen ce, awaren ess of TB sym pt om s an d cont act
t racing for every sp ut um sm ear posit iv e cases, including t hose in ch ild ren, is need ed t o diag nose ch ild hood TB earlier and t o prevent close con t act s
from d ev elopin g adv an ced disease.
Alt hough t h e p roport ion of sp ut um sm ear posit iv e ch ild hood TB cases in our st udy was high, it w as n ot possib le t o confirm t he reliabilit y of our
find ing - in t erm s of diagn ost ic m et hods and result s - due t o t he nat ure of aggregat e dat a in t he hospit al rep ort ing form s as our sou rce of
inform at ion . Con t am inat ion of env ironm ent al m y cobact eria is anot h er reason t hat m ay h av e influ en ced t h is fin din g, wh ich u nderscores t h e
im p ort an ce of cult u re or im m u nological m et hods t o con firm childh ood TB diag nosis.
Classificat ion of TB u sing I CD- 10 syst em posed a part icu lar p roblem becau se of t he difficult ies t o confirm diagn osis of ch ild hood TB. As h igh as
86% of t ot al childh ood TB cases in out pat ien t u nit and 6 9% in inp at ient un it hospit als were foun d t o b e g roup ed as ' unconfirm ed pulm onary TB'
( A15 .1 - A1 6.9) which com bines t h e n um b er of TB cases wit h and wit hout confirm ed cu lt ure, b act eriolog ically, hist ologically or by unsp ecified
m ean s. Howev er, due t o t he nat ure of aggregrat e dat a, it is im possib le t o separat e confirm ed cases from unconfirm ed cases. Classificat ion of TB
cases wit h ou t m en t ion of b act eriolog ical or h ist olog ical confirm at ion" g roup wit hin t he I CD syst em will g en erat e a hig h lev el of false posit iv es or
ov erd iagnosis [ 26] . An exam inat ion of t he discordance bet ween num ber of cases regist ered w it h I CD- 9 diagn ost ic codes and t he act u al num ber of
con firm ed TB cases showed a low p osit ive predict iv e valu e ( 28.6 % ) com pared t o ot h er com m u nicable d iseases [ 2 7] . Av ailabilit y of X- ray facilit ies in
hospit als also increased t he risk for overdiagn osis, esp ecially when t he diag nosis was m ade solely on t h e b asis of u ndefin ed radiolog ic crit eria [ 2 8] .
Fu rt herm ore, in I nd on esian hospit als, t he I CD syst em is m ainly used for billin g pu rp oses, wh ere accu racy of sp ecific diag nosis classificat ion is oft en
neglect ed . Th e p ossibilit y of overdiagn osis can not b e ignored in t his st u dy since it m ight pu t ch ild ren at hig her risk for m ed icat ion error [ 2 9] and
ad verse d ru g effect s [ 8 ] . This issue im p lies t he need for furt her research t o confirm t h e d iagnosis of child h ood TB in hospit als by v alidat ing
childhood TB sign s an d sy m pt om s wit h laborat ory an d rad iological findings as well as im proving I CD- 10 classificat ion for childh ood TB. Desp it e
t h ese lim it at ion s, t h e result from t h is st udy in dicat es a high caseload of ch ild ren d iagnosed as TB in DOTS desig nat ed h osp it als in I ndonesia.
A t ot al of 3 65 cases ( 7.5 % of all childhood TB cases) w ere record ed und er I CD 10 A17. 0 - A19 .0, i.e. EPTB. Th e p roport ion of EPTB in children in
t h is st udy was low com p ared t o t en- y ear cohort s in t h e US and ru ral sout heast Et h iopia wh ich sh ow ed t h at EPTB accoun t ed for 21% and 33% of all
childhood TB, respect iv ely [ 30,3 1] . Using t hese prop ort ions t o est im at e t he t ru e b urden of pulm onary TB am on g children , a 7.5% p roport ion of
EPTB am ong all childh ood TB cases su ggest s a p ossibilit y of over diagn osis of p ulm on ary childhood TB in h osp it als. According t o t h e I CD- 10,
diagn osis of t y pical ch ild hood TB b y observat ion of int ra- t h oracic ly m p h nodes on chest X- ray w as n ot classified as EPTB, bu t as resp irat ory TB. Th is
classificat ion lowers t h e p roport ion of ch ild ren w it h EPTB an d m ay ex plain t he discrepancy wit h findings from ot h er st udies. However, t he I CD- 1 0
syst em does not allow clear classificat ion of in t ra- t horacic d isease ent it ies, which are t he t y pical t y pes of TB encoun t ered in ch ild ren. The chest
X- ray rem ains t he m ost im p ort an t d iagnost ic t ool for childhood TB in lim it ed resou rce set t in gs, t herefore im plem ent at ion of t he proposed
radiolog ical classificat ion of childh ood int ra- t horacic TB is a p ot ent ial way t o im pr ov e t h e classificat ion of ch ild hood TB [ 32] . Howev er, t h is fin din g
cou ld also reflect v ariat ions associat ed wit h t y pes of childhood TB in a high- burden set t ing. Furt her st ud y is need ed t o confirm t his hy pot h esis.
Th e p rogression t o d isease and t he risk of d ev elopin g dissem inat ed form s of TB includ ing m iliary TB and TB of t he nerv ous sy st em are h igh est in
children . Th erefore children wit h d issem in at ed form s of TB need special at t ent ion [ 7,33 ,34] . I n k eep ing wit h t he above fin din g of a low er rat io of
EPTB t o PTB cases t han ex pect ed, m iliary TB cases in our st udy were sligh t ly less com m on ( 0.8 % , 41 out of 482 1 cases) t h an t h at has been
report ed in t he lit erat ure ( 1- 2 % ) [ 3 5] . The m aj orit y ( 6 8% ) occurred am on g y ou nger children , in k eep ing wit h ot her findings w here m ore t han 7 0%
of m iliary TB cases occu rred in children ag ed 0- 4 years [ 17,3 6] . BCG v accinat ion has been kn ow n t o h av e t h e g reat est effect in p rev en t ing sev ere
dissem inat ed d isease in youn g children [ 3 7] . I n t his st ud y, it was not possible t o ret riev e t h e h ist ory of BCG im m un izat ion am on g children. I n
general, cov erage of BCG im m un izat ion in I ndonesia in creased from 7 8% in 200 0 t o 8 9% in 200 5 [ 3 8] .
Conclu sion s
Th e h igh caseload of childhood TB in t hese design at ed DOTS hospit als n ecessit at es in creased at t en t ion wit hin t he NTP. Pub lic h osp it als should be
giv en priorit y in t he im p lem ent at ion of im prov ed childh ood TB case m an ag em en t . Record ing an d rep ort ing of all childhood TB cases diag nosed in
hospit als should t herefore be great ly im prov ed t hrou gh a rev ised int ernat ional disease classificat ion sy st em in ord er t o p rov ide accurat e inform at ion
for plan nin g and m an ag em en t of childh ood TB cont rol p rogram .
List of a bbr e v ia t ions u se d
BCG: Bacillu s Calm et t e- Guérin; DOTS: Direct ly Ob serv ed Treat m ent Short course; EPTB: Ex t ra pulm onary t uberculosis; I CD- 10 : I n t ernat ion al
Classificat ion of Disease version 10 ; I CD- 9 : I n t ernat ion al Classificat ion of Disease version 9; I PT: I son iazid Prop hy laxis Th erapy ; NTP: Nat ion al
Tub erculosis Program ; PTB: Pu lm onary t ub erculosis; TST: Tuberculin Sk in Test ; UK: Unit ed Kin gdom .
Com pe t in g int e re st s
Th e aut hors declare t hat t hey have no com pet ing int erest s.
Aut h or s' cont ribu t ions
TL cont ribu t ed t o t h e init ial concept , desig n, dat a collect ion, coord inat ion and w rit ing of t he m anuscrip t . AP and AU cont ribu t ed t o t h e init ial
con cep t , d esign and dat a collect ion. TL, AP, AKH an d AU cont ribut ed t o t he in t erpret at ion of d at a. All aut hors com m ent ed on t h e m an uscript and
gave approval for final su bm ission.
Ack n ow le dge m e n t s
We t hank t h e h osp it als inv olv ed , t h e Nat ion al TB Prog ram in I n donesia, an d t he field st aff for t heir m et iculous fieldwork. We also t hank Ann a Ralp h,
Hans L. Ried er, Tari Turner, Yodi Mahendradhat a, and Pat rick Vau ghan, for t h eir crit ical review s of t he m anu script an d useful com m ent s. Th e p roj ect
was supp ort ed by t h e Su b Direct orat e of Tu bercu losis, Minist ry of Healt h Repu blic of I ndonesia and fu nded b y t he Dep art m ent for I n t ernat ion al
Dev elop m ent , UK Gov ernm en t , t hrough WHO I ndonesia, proj ect no. I NO TUB 0 02 XW 06 EC0. P01. A0 1.
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Pre - pu blica tion h istory
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H igh ca se loa d of ch ildh ood tu be rcu losis in h ospita ls on Ja va I sla n d, I n don e sia : a cross
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Abstr a ct
Ba ck g rou n d
Childhood t uberculosis ( TB) has been neglect ed in t he fig ht ag ainst TB. Despit e im p lem ent at ion of Direct ly Observ ed Treat m ent Short course
( DOTS) p rogram in pub lic and priv at e hospit als in I nd on esia since 200 0, t he burden of childh ood TB in hospit als was largely unk nown . Th e g oals of
t h is st udy were t o docum ent t he caseload and t y pes of ch ild hood TB in t he 0- 4 an d 5- 1 4 y ear age grou ps diag nosed in DOTS h osp it als on Java
I sland , I nd on esia.
M e t h od s
Cross- sect ional st udy of TB cases record ed in inpat ient an d out pat ien t regist ers of 3 2 hospit als. Cases w ere an alyzed b y h osp it al charact erist ics,
ag e g roup s, an d t yp es of TB. Th e n um b er of cases rep ort ed in t he out pat ien t u nit was com pared wit h t hat record ed in t he TB regist er.
Re su lt s
Of 5 ,877 TB cases in t he in pat ien t u nit and 1 5,69 4 in t h e out pat ient unit , 1 1% ( 6 48) an d 27 % ( 4,1 73) respect iv ely w ere children . Most of t he
childhood TB cases were u nder fiv e y ears old ( 56% and 53% in t he inp at ient and out pat ient clin ics resp ect iv ely ) . The prop ort ion of sm ear posit iv e
TB w as t wice as high in t he inp at ient com pared t o t he ou t p at ient un it s ( 15 .6% v s 8.1% ) . Ex t ra- pu lm onary TB accou nt ed for 15 % an d 6% of TB
cases in inp at ient and out pat ient clin ics resp ect iv ely. Am on g children recorded in hospit als only 1.6 % were rep ort ed t o t he Nat ional TB Program .
Con clu sion
I n response t o t he hig h caseload and gross u nder- rep ort ing of ch ild hood TB cases, t h e Nat ion al TB Prog ram sh ou ld g iv e h igh er priorit y for childhood
TB case m anagem ent in d esignat ed DOTS hospit als. I n ad dit ion, an int ernat ional gu idan ce on childh ood TB recordin g and report in g and im proved
diagn ost ics and st and ardized classificat ion is required
Ba ck groun d
Childhood t uberculosis ( TB) has been neglect ed in t he glob al effort s t o con t rol TB, [ 1,2 ] because it is consid ered t o b e rarely cont ag ious and
difficult t o d iagnose. I t is difficult t o con firm on bact eriological ex am in at ion of spu t u m , not ab ly if only m icroscopy is availab le [ 3,4 ] .
Th e WHO est im at ed t hat 11% of all n ew TB cases diagn osed in 20 00 w ere children [ 5] . Th e p roport ion is higher in h igh TB- burden coun t ries,
reflect ing t h at childh ood TB rep resent s act iv e TB t ran sm ission wit hin a com m un it y. A recent t uberculin surv ey est im at ed t hat 3.2% t o 6.8% of all
children in Cent ral Java Prov ince hav e TB in fect ion [ 6] . The proport ions est im at ed for low- an d m iddle- incom e count ries rang e from 15 % t o 4 0 % of
all TB cases, wh ile it accou nt ed on ly for 0.2 % t o 6% of not ified n ew sput um sm ear posit iv e ( SS+ ) cases from 22 h igh burden coun t ries [ 5 ,7] .
Howev er, t h e n um b er of not ified childh ood TB cases m ay not reflect t h e t rue burden of childh ood TB because of t he in ad eq uacy of exist ing
surveillance syst em s and p oorly docum ent ed dat a [ 8] . The WHO guidelin es h av e already requ est ed count ries t o rep ort child TB dat a in t w o age
grou ps ( 0 - 4 and 5- 1 4 y ears old) , h ow ev er, v ery few cou nt ries com p ly [ 9] .
Sim ilar t o ot her hig h bu rd en cou nt ries, I ndonesia faces ch allenges in cap t u ring ch ild hood TB cases t o be t reat ed u nder t h e Nat ion al TB Prog ram
( NTP) . Before t he int rod uct ion of a scoring chart as a st andardized app roach t o t he d iag nosis of childhood TB in 2 007 , t h e d iagnosis of childh ood TB
was based on chest X- ray and/ or TB sign s an d sy m pt om s. The scorin g chart com p rises h ist ory of cont act w it h a sm ear spu t u m posit iv e case,
posit iv e t ub erculin sk in t est ( TST) , weigh t , fev er, cou gh, lym ph enlargem ent , bone an d j oin t enlargem ent s, and su ggest iv e ch est X- ray [ 10 ] .
Howev er, t h e sensit ivit y and sp ecificit y of t he I n donesian scoring ch art have not been validat ed and t h e cost for TST t est is st ill h igh an d only
av ailable at hospit als and ch est clinics.
Despit e im plem ent at ion of Direct ly Observed Treat m en t Sh ort - course ( DOTS) st rat eg y in hospit als since 200 0 [ 1 1] , t he bu rd en of ch ild hood TB in
t h ese hospit als w as largely un kn ow n. The goals of t his st u dy were t o d ocu m ent t h e caseload an d t yp es of childh ood TB in t h e 0 - 4 and 5- 1 4 y ear
ag e g roup s diagn osed in DOTS hospit als on Jav a I sland , I nd on esia.
M e t h ods
Th is is a cross- sect ional st ud y t hat was part of a larger research on assessm ent of t he im plem ent at ion of DOTS st rat egy in h osp it als in Jav a I sland ,
I nd on esia. The st udy was condu ct ed from 1 Au gust 20 06 t o 31 May 20 07 in all six p rov inces of Java t o collect TB dat a from cases diag nosed in
200 5 t o ensu re t hat all pat ien t s h ad com plet ed t h eir t reat m ent .
I n 2 005 , a t ot al of 15 3 ( 3 1% ) h osp it als on Java I slan d were t rained in DOTS st rat egy by t he NTP an d t he hospit als were d esignat ed as DOTS
hospit als. One hun dred an d one DOTS hospit als were select ed t h roug h qu ot a sam pling an d st rat ified based on bed capacit y ( large an d sm all) ,
ow nersh ip ( pub lic and priv at e) , and t each ing funct ion ( t eachin g and n on - t eaching) . Th ree hospit als declined t o p art icip at e for adm inist rat iv e
reason s. I nclusion crit eria for a su b- st ud y on caseload of ch ild hood TB w ere t h e av ai labilit y of a st and ardized hospit al m orbid it y report in inp at ient
an d out pat ien t u nit s, and a TB regist er for t he year 2 005 . On ly 32 h osp it als m et t hese inclusion crit eria and were select ed for t h e st ud y. These
hospit al charat erist ics, i.e. bed capacit y, ownership an d t eaching fu nct ion were n ot sig nifican t ly d ifferent from t h e h osp it al populat ion ( p 0.1 , 0.1
and 0.4 respectively, α = 5%).
A half- d ay m eet ing w as cond uct ed in each province t o exp lain t he st udy 's p urpose and prot ocol. On e represent at ive from each h osp it al was
ap point ed as t h e cont act p erson resp on sible for con firm in g t he av ailabilit y of d at a n eed ed . A t rained research assist an t w as t hen sent t o each
hospit al for t hree d ay s t o collect TB dat a in 200 5.
Th e research assisst an t s collect ed dat a on: ( 1) Hospit al p rofiles ( hospit al size, own ership an d t eaching st at u s) , wh ich w ere collect ed from a
self- adm inist ered q uest ion naire; ( 2) Dat a on TB cases am ong ad ult s and ch ild ren w ere ob t ain ed from t he hospit al m orbidit y report for t h e inpat ient
( RL2A) an d t he ou t p at ient un it ( RL2B) an d ( 3 ) Dat a on TB cases regist ered in t he DOTS program ( TB 03) .
RL2A and RL2 B are t h e n at ional st andardized form s cont ainin g t he ag greg at ed dat a report in g hospit al m orbidit y, w hich are grou ped based on t he
I nt ern at ional Code of Disease version 10 ( I CD- 1 0) . I n t hese report s, TB is coded un der I CD- 10 A1 5.0 - A19.0 , an d classified furt h er in t o nine grou p
of d iseases, i.e. sm ear sp ut um p osit ive TB ( A15 .0) , ot her p ulm on ary TB ( A15.1 - A16 .2) , respirat ory t ract TB ( A16 .3- 9 ) , m eningit is TB ( A17.0 ) ,
ot her cen t ral nervous sy st em TB ( A17.1 - A17 .9) , b on e and j oint TB ( A18.0 ) , ly m p haden it is TB ( A1 8.2) , m iliary TB ( A19 ) and ot her TB ( A1 8.1,
A18.3 , A18.8 ) . Wit h in t he 'ot her p ulm on ary TB' grou p in t h e RL2 A an d RL2B form s ( A1 5. 1- A16.2 ) , bact eriologically, h ist olog ically, or cult u re
con firm ed TB cases ( A1 5.1 t o A15.9 ) were com b ined w it h un con firm ed TB cases ( A1 6.1 t o A16.2 ) . Therefore, it was not possible t o calculat e all
con firm ed TB cases from t h e h osp it al m orb idit y rep ort . We t reat ed t his grou p as uncon firm ed cases because t h e cu rrent pract ice in diagn osing
childhood TB in I ndonesia rarely used bact eriologically, h ist olog ically or cu lt ure confirm at ion. To sim plify ou r analy sis, w e fu rt her com bin ed 'ot h er
pulm onary TB' ( A1 5.1 - A16.2 ) and ' ot her respirat ory TB' ( A16 .3 - A1 6.9) grou ps in t o 'u nconfirm ed p ulm on ary TB" ( A15 .1 - A1 6.9) . We also
com bin ed differen t g roup s of ex t ra- pu lm onary TB ( A1 7.0, A1 7.1 - A17.9 , A18.1 - 3, A1 8.8 , and A19.0 ) in t o one grou p of 'EPTB' ( A1 7.0 - A19.0 ) .
Th erefore, we have t hree groups of disease classificat ion in t h is st udy, i.e. t u bercu losis of lun g, confirm ed b y sp ut um m icroscopy wit h or wit h ou t
cult ure ( A15 .0) , u nconfirm ed p ulm on ary TB ( A15.1 - A16 .9) , and ex t ra- p ulm on ary TB ( A1 7.0 - A19 .0) . Due t o t he nat ure of t he ag greg at e dat a
sou rces, it was not possible t o verify t h e d iagnost ic m et hods in ind iv idu al cases and t o con firm t he diagn osis of TB.
I n I ndonesia, hospit als are m ainly classified accordin g t o t he nu m ber of b ed s av ailab le, own ership, and t each ing cap acit y. Large and sm all, pu blic
an d priv at e, or t each ing an d non- t eachin g hospit al feat u re un iqu e com p lexit ies in t he im p lem ent at ion of DOTS program . Th e ch i- sq uare t est and
t w o- prop ort ion z- t est w ere used t o calcu lat e differences bet w een g roup s of ch ild hood TB in different t y pes of hospit als, t yp es of TB, an d age grou ps
accordin g t o t he WHO recom m end at ion ( i.e. 0- 4 an d 5- 14 y ear- old ) . The find ing s are su m m arized separat ely for in pat ien t s and ou t p at ient s. We
div id ed t h e n um b er of childhood TB cases in t h e TB reg ist er by t he t ot al num ber of ch ildh ood TB cases recorded in t he hospit al m orbid it y report in
t h e inpat ient an d out pat ien t u nit t o obt ain t he proport ion of childh ood TB t reat ed u n der t h e DOTS st rat egy. St at ist ical an alyses were carried ou t
usin g Ep i I n fo soft ware v ersion 3 .3.2 and Microsoft Ex cel.
Et hical app rov al was ob t ain ed from t he Et hics Com m it t ee, Facult y of Med icin e, Un iv ersit as Gadj ah Mad a. Perm ission t o con duct t he st u dy was
receiv ed from each hospit al.
Re su lt
Un d e rre p ort in g of ch ild h ood TB t re a t e d u n d e r t h e D OTS st ra t e g y
I n 2 005 , a t ot al of 4,8 21 ch ild ren ( 648 in t he in pat ien t u nit and 4 ,173 in t he out pat ien t u nit s) w ere diagn osed as TB pat ien t s in 32 hospit als on
Java I slan d. How ev er, t here was a larg e d iscrep an cy b et ween t he num ber of childh ood TB cases b eing d iagnosed in t h e h osp it al an d t hose t hat
were act u ally report ed t o t h e NTP. Out of 3 2 hospit als, only 1 1 hospit als recorded ch ild hood TB in t heir TB regist ry ( TB0 3 form ) . Overall, only 75 ou t
of 4 ,821 ( 1.6 % ) childh ood TB cases in hospit als w ere act ually recorded in t he TB regist ers and report ed t o t h e NTP. The m aj orit y of cases report ed
were 5 t o 14 y ears old ( 75% ) an d classified as p ulm on ary cases ( 6 5% ) . Sp ut um sm ear ex am in at ion w as carried ou t in 39 cases ( 5 2% ) , and 9
( 23 % ) were p osit ive. Only one case receiv ed child friend ly an t i TB form ulat ions, and t h e rest received a st an dard ad ult reg im en.
Prop ort ion of ch ild h ood TB ca se s a m on g a ll TB ca se s
Children con st it u t ed 1 1% and 2 7% of all TB cases in t h e inpat ient an d out pat ien t u nit s, resp ect iv ely. Tab le 1 shows t he caseload of childh ood TB by
hospit al t yp e. I n in pat ien t u nit s, t he prop ort ion of childhood TB was sign ificant ly h igher in larger an d t eaching h osp it als ( p < 0.01 ) , bu t d id n ot
differ sign ificant ly by hospit al own ership. I n con t rast , am ong ou t p at ient un it s, t h e p roport ion of ch ild hood TB w as significant ly larg er ( p < 0.0 1) in
sm all and non- t each ing hospit als, as well as in pub lic h osp it als.
T ab le 1 . Caseload of ch ild hood TB in different t y pes of hospit als
Table 2 d escrib es caseload an d t yp es of childh ood TB based on age grou ps in t h e inpat ient an d out pat ien t u nit s. The m aj orit y of ch ild hood TB cases
in t he in pat ien t u nit were ch ild ren aged 0 - 4 y ears ( 5 6% ) . I n reg ards t o TB t y pes, m ost w ere classified as un con firm ed pu lm onary TB ( 6 9% ) . The
prop ort ion of t h ose wit h sput um sm ear or cu lt ure p osit ive TB an d EPTB was eq ual, i.e. 16 % an d 15 % . Children wit h sp ut um sm ear posit iv e TB
con t rib ut ed up t o 5% of all spu t u m sm ear p osit ive TB cases t reat ed in t he inp at ient u n it an d 20 % of t hese children ( 20 ou t of 10 1 cases) were less
t h an fiv e y ears old. There w ere no differen ces in t he dist ribu t ion of EPTB bet ween ag e g roup s ( p = 0.08 ) .
T ab le 2 . Typ es and prop ort ion of childhood TB in inpat ient an d out pat ien t u nit
Th e findings also showed t hat t h e p roport ion of ch ild hood TB cases und er fiv e years old in t he out pat ien t u nit s was slight ly higher t h an in t he
inp at ient un it s ( 53 % in out pat ient unit s, 5 6% in inp at ient un it s) . I n som e g en eral hospit als, t he nu m ber of out pat ient childhood TB cases
surpassed t h e n um b er of ad ult TB cases ( d at a not sh ow n) . The m aj orit y of cases were classified as 'un con firm ed pu lm onary TB' ( 86% ) , followed by
sput um sm ear posit iv e TB ( 8% ) and EPTB ( 6% ) . The proport ion of children wit h sput um sm ear posit iv e TB out of all spu t u m sm ear p osit ive TB
cases t reat ed at t h e out pat ient unit w as 1 6% , t hree t im es higher t h an it s prop ort ion in t h e inpat ient unit and m ore t han half ( 52% ) were below five
years of age.
Table 3 d escrib es t y pes of EPTB in t h ree m aj or groups accord ing t o I CD 10 classificat ion, i. e. TB of t he nervous sy st em ( A17 , 36% ) , TB of ot h er
organs ( A18, 5 2% ) and m iliary TB ( A19 , 11.2 % ) . Tu bercu losis of t h e n erv ou s syst em in t h e inpat ient an d out pat ien t u nit was dom inat ed b y
m enin git is TB ( 9 5% , dat a n ot shown ) and occurred eq ually at d ifferent age grou ps. Tu b ercu losis periph eral ly m p hadenopat h y w as t he m ost
com m on t yp e of TB of ot her organs ( 6 4% ) and m ost ly occurred am on g older children . Mil iary TB was pred om inant am ong y oung children ( 68 % ) .
T ab le 3 . Typ es of ext ra- pulm onary t uberculosis
Discu ssion
Ou r st ud y ident ified t wo m ain find ing s: first ly, t he high p roport ion of ch ild ren d iag nosed wit h TB in all t y pes of h osp it als t h roug hout Java islan d;
an d secon dly, gross u nder report ing of childh ood TB cases t reat ed in t he DOTS desig nat ed h osp it al t o t he NTP.
A key find ing report ed in t his st ud y is t h e fact t h at only 11 ou t of 32 t rained h osp it als im p lem ent ing t h e DOTS st rat egy record ed childhood cases in
t h e st andardized TB reg ist er and report ed t hem t o t he NTP. Th e t ot al n um b er of regist ered childhood TB cases was only 1.6 % of all childhood TB
cases t reat ed in hospit als, indicat in g a poor disease surveillance syst em for ch ild hood TB in t he cou nt ry. Th is ph en om en on is not unique t o
I nd on esia, as weak su rv eillan ce d at a for childh ood TB in m any ot her cou nt ries is com m on du e t o difficult y in d iagnosis, and as a resu lt , lim it ed
childhood TB ep idem iolog ical st udies h av e been con duct ed. Ev en in a w ell- resou rced coun t ry such as in t h e UK, an est im at ed 20% of all ch ild hood
TB cases in 2 004 were not report ed t o t h e TB surv eillance sy st em [ 12] . I n Sout h Africa, only 56 % of m en ing it is TB cases were report ed t o t he NTP
[ 13 ] . This sit u at ion reflect s t he perceived low priorit y of childhood TB in g en eral, and w eak int ern al lin kage wit h pediat ric unit s in t he
im p lem ent at ion of t he DOTS st rat egy in hospit als.
Con seq uent ly, NTP is unlik ely t o accu rat ely capt ure t h e b urden of childhood TB, im p ai ring accurat e plan nin g and m an ag em en t , inclu din g logist ics,
i.e. t h e su pply of child- frien dly ant i TB drugs in DOTS hospit als. The fact t hat on ly on e report ed case received ant i TB drug s from t he NTP m ay
illust rat e t he lim it ed use of child- friend ly an t i TB d ru gs in hospit als, and t herefor e n on - st an dard ized TB drug form ulat ions are cont in uously
prescrib ed .
Th e p roport ion of ch ild hood TB in t he ou t p at ient un it was t en t im es h igh er t han t he est im at ed proport ion of all t y pes of ch ild hood TB for t h e
I nd on esian populat ion ( 27% v s 2.7 % ) . This finding, h ow ev er, corresponds w ell wit h t h e est im at ed childhood TB caseload in low and m idd le- in com e
cou nt ries, w hich rang ed from 1 5% t o 4 0% of all TB cases [ 7 ] . I n Java I slan d, hospit als rem ain t o be t h e first healt h provider of choice. Half of
households w it h previou s TB h ist ory survey ed in t he Nat ional TB Prev alen ce Su rv ey 2 00 4 chose h osp it als for TB t reat m ent [ 1 4] . Furt her analy sis of
childhood TB caseloads in differen t h osp it al charact erist ics su ggest t h at bu rd en of p ublic hospit als w ere hig her com p ared t o p rivat e h osp it als. Cases
referred t o h osp it al also t end t o be m ore severe com p ared t o ot her h ealt h facilit ies, such as prim ary healt h care. Th erefore it is m ore lik ely t o det ect
TB cases in h osp it al. Hence, our result cann ot be ext rap olat ed t o t he general populat ion d ue t o pot en t ial select ion b ias.
Con sist en t w it h fin din gs from ot her st u dies,[ 1 5- 1 9] m ore t h an half of childhood TB cases occurred in t he ag e g roup of 0 - 4 y ears ( i.e. 5 6% in t h e
inp at ient and 5 3% in t h e out pat ient unit ) . High incid en ce of TB am on g children un der five y ears of age in dicat es ong oing d isease t ransm ission in
t h e h ou seh old [ 2 0] . This can be prev ent ed wit h t he provision of I soniazid Prophy lax is Therapy ( I PT) in approxim at ely 60 % of at - risk ind iv idu als
[ 21 ] . Accord ing t o t he WHO recom m endat ion, I PT should be giv en for six m on t h s t o children aged less t han fiv e years w ho are household cont act s
of infect iou s cases [ 9 ,22] . I n I ndonesia, howev er, con t act t racing an d provision of TB p roph ylax is t o hig h- risk children are st ill rarely im plem en t ed.
Con t rary t o t he usu al op inion , t h e p roblem of ch ild hood TB also poses a serious pu bli c healt h issue du e t o a h igh prop ort ion of SS+ TB seen in
children in t his st u dy. These cases are as infect ious as sput um sm ear posit iv e ad ult TB cases and t hey can be t h e source of infect ion s for ot h er
children [ 20 ] . The WHO est im at ed t h at t he prop ort ion of children wit h sp ut um sm ear posit iv e TB am ong all not ified spu t u m sm ear p osit ive TB
cases for I ndonesia ran ged from 0.2% t o 4.8% , w it h an est im at ed p roport ion of 1 .1% [ 5 ] . I n ou r st ud y, t he prop ort ion in hospit als was higher, u p t o
5% in t h e inpat ient unit and 16% in t he ou t p at ient un it . Th e p roport ion of sm ear posit iv e cases am on g childh ood TB cases report ed t o t he NTP was
ev en higher ( 23 % or 9 out of 39 ch ild hood TB cases wit h sm ear sput um result ) . Anot h er st udy in hig h endem ic set t ing s fou nd a proport ion of 5.8 %
of all childhood TB were sm ear p osit ive in t h e Kilim an j aro region [ 15 ] , 5% in Malawi,[ 19 ] 4.7 % in I ndia [ 23] , an d 20 % in Thailan d [ 2 4] . This
find ing challeng es a com m on p ercept ion t hat y oung children wit h TB are rarely con t agi ou s [ 25 ] . Hen ce, awaren ess of TB sym pt om s an d cont act
t racing for every sp ut um sm ear posit iv e cases, including t hose in ch ild ren, is need ed t o diag nose ch ild hood TB earlier and t o prevent close con t act s
from d ev elopin g adv an ced disease.
Alt hough t h e p roport ion of sp ut um sm ear posit iv e ch ild hood TB cases in our st udy was high, it w as n ot possib le t o confirm t he reliabilit y of our
find ing - in t erm s of diagn ost ic m et hods and result s - due t o t he nat ure of aggregat e dat a in t he hospit al rep ort ing form s as our sou rce of
inform at ion . Con t am inat ion of env ironm ent al m y cobact eria is anot h er reason t hat m ay h av e influ en ced t h is fin din g, wh ich u nderscores t h e
im p ort an ce of cult u re or im m u nological m et hods t o con firm childh ood TB diag nosis.
Classificat ion of TB u sing I CD- 10 syst em posed a part icu lar p roblem becau se of t he difficult ies t o confirm diagn osis of ch ild hood TB. As h igh as
86% of t ot al childh ood TB cases in out pat ien t u nit and 6 9% in inp at ient un it hospit als were foun d t o b e g roup ed as ' unconfirm ed pulm onary TB'
( A15 .1 - A1 6.9) which com bines t h e n um b er of TB cases wit h and wit hout confirm ed cu lt ure, b act eriolog ically, hist ologically or by unsp ecified
m ean s. Howev er, due t o t he nat ure of aggregrat e dat a, it is im possib le t o separat e confirm ed cases from unconfirm ed cases. Classificat ion of TB
cases wit h ou t m en t ion of b act eriolog ical or h ist olog ical confirm at ion" g roup wit hin t he I CD syst em will g en erat e a hig h lev el of false posit iv es or
ov erd iagnosis [ 26] . An exam inat ion of t he discordance bet ween num ber of cases regist ered w it h I CD- 9 diagn ost ic codes and t he act u al num ber of
con firm ed TB cases showed a low p osit ive predict iv e valu e ( 28.6 % ) com pared t o ot h er com m u nicable d iseases [ 2 7] . Av ailabilit y of X- ray facilit ies in
hospit als also increased t he risk for overdiagn osis, esp ecially when t he diag nosis was m ade solely on t h e b asis of u ndefin ed radiolog ic crit eria [ 2 8] .
Fu rt herm ore, in I nd on esian hospit als, t he I CD syst em is m ainly used for billin g pu rp oses, wh ere accu racy of sp ecific diag nosis classificat ion is oft en
neglect ed . Th e p ossibilit y of overdiagn osis can not b e ignored in t his st u dy since it m ight pu t ch ild ren at hig her risk for m ed icat ion error [ 2 9] and
ad verse d ru g effect s [ 8 ] . This issue im p lies t he need for furt her research t o confirm t h e d iagnosis of child h ood TB in hospit als by v alidat ing
childhood TB sign s an d sy m pt om s wit h laborat ory an d rad iological findings as well as im proving I CD- 10 classificat ion for childh ood TB. Desp it e
t h ese lim it at ion s, t h e result from t h is st udy in dicat es a high caseload of ch ild ren d iagnosed as TB in DOTS desig nat ed h osp it als in I ndonesia.
A t ot al of 3 65 cases ( 7.5 % of all childhood TB cases) w ere record ed und er I CD 10 A17. 0 - A19 .0, i.e. EPTB. Th e p roport ion of EPTB in children in
t h is st udy was low com p ared t o t en- y ear cohort s in t h e US and ru ral sout heast Et h iopia wh ich sh ow ed t h at EPTB accoun t ed for 21% and 33% of all
childhood TB, respect iv ely [ 30,3 1] . Using t hese prop ort ions t o est im at e t he t ru e b urden of pulm onary TB am on g children , a 7.5% p roport ion of
EPTB am ong all childh ood TB cases su ggest s a p ossibilit y of over diagn osis of p ulm on ary childhood TB in h osp it als. According t o t h e I CD- 10,
diagn osis of t y pical ch ild hood TB b y observat ion of int ra- t h oracic ly m p h nodes on chest X- ray w as n ot classified as EPTB, bu t as resp irat ory TB. Th is
classificat ion lowers t h e p roport ion of ch ild ren w it h EPTB an d m ay ex plain t he discrepancy wit h findings from ot h er st udies. However, t he I CD- 1 0
syst em does not allow clear classificat ion of in t ra- t horacic d isease ent it ies, which are t he t y pical t y pes of TB encoun t ered in ch ild ren. The chest
X- ray rem ains t he m ost im p ort an t d iagnost ic t ool for childhood TB in lim it ed resou rce set t in gs, t herefore im plem ent at ion of t he proposed
radiolog ical classificat ion of childh ood int ra- t horacic TB is a p ot ent ial way t o im pr ov e t h e classificat ion of ch ild hood TB [ 32] . Howev er, t h is fin din g
cou ld also reflect v ariat ions associat ed wit h t y pes of childhood TB in a high- burden set t ing. Furt her st ud y is need ed t o confirm t his hy pot h esis.
Th e p rogression t o d isease and t he risk of d ev elopin g dissem inat ed form s of TB includ ing m iliary TB and TB of t he nerv ous sy st em are h igh est in
children . Th erefore children wit h d issem in at ed form s of TB need special at t ent ion [ 7,33 ,34] . I n k eep ing wit h t he above fin din g of a low er rat io of
EPTB t o PTB cases t han ex pect ed, m iliary TB cases in our st udy were sligh t ly less com m on ( 0.8 % , 41 out of 482 1 cases) t h an t h at has been
report ed in t he lit erat ure ( 1- 2 % ) [ 3 5] . The m aj orit y ( 6 8% ) occurred am on g y ou nger children , in k eep ing wit h ot her findings w here m ore t han 7 0%
of m iliary TB cases occu rred in children ag ed 0- 4 years [ 17,3 6] . BCG v accinat ion has been kn ow n t o h av e t h e g reat est effect in p rev en t ing sev ere
dissem inat ed d isease in youn g children [ 3 7] . I n t his st ud y, it was not possible t o ret riev e t h e h ist ory of BCG im m un izat ion am on g children. I n
general, cov erage of BCG im m un izat ion in I ndonesia in creased from 7 8% in 200 0 t o 8 9% in 200 5 [ 3 8] .
Conclu sion s
Th e h igh caseload of childhood TB in t hese design at ed DOTS hospit als n ecessit at es in creased at t en t ion wit hin t he NTP. Pub lic h osp it als should be
giv en priorit y in t he im p lem ent at ion of im prov ed childh ood TB case m an ag em en t . Record ing an d rep ort ing of all childhood TB cases diag nosed in
hospit als should t herefore be great ly im prov ed t hrou gh a rev ised int ernat ional disease classificat ion sy st em in ord er t o p rov ide accurat e inform at ion
for plan nin g and m an ag em en t of childh ood TB cont rol p rogram .
List of a bbr e v ia t ions u se d
BCG: Bacillu s Calm et t e- Guérin; DOTS: Direct ly Ob serv ed Treat m ent Short course; EPTB: Ex t ra pulm onary t uberculosis; I CD- 10 : I n t ernat ion al
Classificat ion of Disease version 10 ; I CD- 9 : I n t ernat ion al Classificat ion of Disease version 9; I PT: I son iazid Prop hy laxis Th erapy ; NTP: Nat ion al
Tub erculosis Program ; PTB: Pu lm onary t ub erculosis; TST: Tuberculin Sk in Test ; UK: Unit ed Kin gdom .
Com pe t in g int e re st s
Th e aut hors declare t hat t hey have no com pet ing int erest s.
Aut h or s' cont ribu t ions
TL cont ribu t ed t o t h e init ial concept , desig n, dat a collect ion, coord inat ion and w rit ing of t he m anuscrip t . AP and AU cont ribu t ed t o t h e init ial
con cep t , d esign and dat a collect ion. TL, AP, AKH an d AU cont ribut ed t o t he in t erpret at ion of d at a. All aut hors com m ent ed on t h e m an uscript and
gave approval for final su bm ission.
Ack n ow le dge m e n t s
We t hank t h e h osp it als inv olv ed , t h e Nat ion al TB Prog ram in I n donesia, an d t he field st aff for t heir m et iculous fieldwork. We also t hank Ann a Ralp h,
Hans L. Ried er, Tari Turner, Yodi Mahendradhat a, and Pat rick Vau ghan, for t h eir crit ical review s of t he m anu script an d useful com m ent s. Th e p roj ect
was supp ort ed by t h e Su b Direct orat e of Tu bercu losis, Minist ry of Healt h Repu blic of I ndonesia and fu nded b y t he Dep art m ent for I n t ernat ion al
Dev elop m ent , UK Gov ernm en t , t hrough WHO I ndonesia, proj ect no. I NO TUB 0 02 XW 06 EC0. P01. A0 1.
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Th e p re- p ublicat ion hist ory for t his paper can b e accessed here:
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