Paediatrica Indonesiana

Paediatr Indones, Vol. 54, No. 5, September 2014

285VOLUME 54

September

NUMBER 5

Original Article

Anti-S. typhi Vi IgG levels in children with and without typhoid vaccinations

Abstract

Sriandayani, Tonny H. Rampengan, Hesti Lestari, Novie Rampengan

7yphoid fever is an acute, life-threateningBackground 7\SKRLG IHYHU LV HQGHPLF WR ,QGRQHVLD ZLWK DQ DQQXDO LQFLGHQFH RI SHRSOH 9DFFLQDWLRQ KDV EHHQ VKRZQ WR EH DQ HIIHFWLYH PHWKRG WR SUHYHQW W\SKRLG IHYHU 2I VHYHUDO YDFFLQH W\SHV the polysaccharide Vi vaccine is the most commonly used typhoid YDFFLQH LQ GHYHORSLQJ FRXQWULHV 5HVXOWV RI SUHYLRXV VWXGLHV UHPDLQ LQFRQFOXVLYH RQ WKH QHFHVVLW\ RI UHYDFFLQDWLRQ HYHU\ \HDUV Objective 7R FRPSDUH WKH PHDQ VHUXP DQWLERG\ WLWHUV RI DQWL S. typhi 9L ,J* DQG WKH SURSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQWLERG\ OHYHOV EHWZHHQ FKLOGUHQ ZLWK DQG ZLWKRXW W\SKRLG 9L YDFFLQDWLRQ Methods :H FRQGXFWHG D FURVV VHFWLRQDO VWXG\ DW 7XPLQWLQJ 'LVWULFW 0DQDGR IURP -XQH WR 6HSWHPEHU 'DWD ZDV DQDO\]HG XVLQJ LQGHSHQGHQW 7 WHVW DQG )LVKHUV WHVW 6HUXP DQWL S. typhi Vi,J* OHYHOV ZHUH PHDVXUHG E\ enzyme-linked immunosorbent assay (/,6$ PHWKRG Results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onclusion 7KH PHDQ VHUXP DQWL S. typhi Vi IgG antibody level in FKLOGUHQ ZKR KDG EHHQ YDFFLQDWHG PRUH WKDQ \HDUV SULRU WR WKH VWXG\ LV KLJKHU WKDQ LQ FKLOGUHQ ZKR KDG QHYHU UHFHLYHG W\SKRLG YDFFLQDWLRQV 1HYHUWKHOHVV WKH PHDQ DQWLERG\ WLWHUV DUH JHQHUDOO\ QRQ SURWHFWLYH LQ ERWK JURXSV $OVR WKH SURSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQWLERG\ OHYHOV LV QRW VLJQLILFDQWO\ GLIIHUHQW EHWZHHQ WKH WZR JURXSV [Paediatr Indones. 2014;54:284-8.]

Keywords: anti-S. typhi Vi IgG, Vi polysaccharide typhoid vaccine, typhoid fever, children

disorder commonly characterized by fever, headache, malaise, anorexia, spleenHQODUJHPHQW DQG UHODWLYH EUDG\FDUGLD 7\SKRLG IHYHU LV UHFRJQL]HG DV D PDMRU KHDOWK problem due to its rapid spread, especially in dense SRSXODWLRQV 7KH World Health Organization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ata collected from Department of Pediatrics,3URI 'U 5 ' .DQGRX *HQHUDO +RVSLWDO IURP WR VKRZV WKDW WKH QXPEHU RI W\SKRLG FDVHV ZDV WR RXW RI LQSDWLHQWV 7KH H[WHQW RI WKH W\SKRLG IHYHU EXUGHQ KDV

From the Department of Child Health, Sam Ratulangi University0HGLFDO 6FKRRO 0DQDGR ,QGRQHVLD

Reprint requests to 6ULDQGD\DQL 'HSDUWPHQW RI &KLOG +HDOWK 6DP 5DWXODQJL 8QLYHUVLW\ 0HGLFDO 6FKRRO -O 5D\D 7DQDZDQJNR QR 3 2 %R[ 0DODOD\DQJ 0DQDGR ,QGRQHVLD 7HO )D[ ( PDLO SHGLVLX#\DKRR FRm

Sriandayani et al: $QWL 6 W\SKL 9L ,J* OHYHOV LQ FKLOGUHQ ZLWK DQG ZLWKRXW W\SKRLG YDFFLQDWLRQV

raised the necessity for an effective prevention VWUDWHJ\ VXFK DV YDFFLQDWLRQ 7R GDWH WKHUH DUH WZR LQWHUQDWLRQDOO\ UHFRPPHQGHG W\SKRLG YDFFLQHV WKH 9L SRO\VDFFKDULGH YDFFLQH DQG WKH OLYH DWWHQXDWHG 7\ D YDFFLQH 7KH 9L SRO\VDFFKDULGH YDFFLQH KDV EHHQ PRVW ZLGHO\ XVHG LQ FRXQWULHV ZLWK D KLJK LQFLGHQFH RI W\SKRLG Studies have reported that the cumulative efficacy of the Vi polysaccharide vaccine lasts only for WR \HDUV WKHUHIRUH UHYDFFLQDWLRQ LV QHHGHG HYHU\ \HDUV +RZHYHU RWKHU VWXGLHV ZLWK GLIIHULQJ UHVXOWV KDYH DUJXHG DJDLQVW WKH QHFHVVLW\ RI UHYDFFLQDWLRQ 7R GDWH QR VWXG\ KDV EHHQ FRQGXFWHG LQ 0DQDGR regarding the protective response of the typhoid YDFFLQH ZKHUHDV WKH FRQWUDGLFWRU\ UHVXOWV RI SUHYLRXV studies implicitly indicated that the quality of UHVSRQVH WR W\SKRLG YDFFLQDWLRQ ZHUH YDU\ LQ GLIIHUHQW JHRJUDSKLFDO DUHDV 7KHVH GLIIHUUHQFHV PDLQO\ UHODWHG WR GHJUHH RI HQGHPLFLW\ RI HDFK SDUWLFXODU UHJLRQ $FFRUGLQJO\ ZH FRQGXFW WKLV VWXG\ WR FRPSDUH WKH anti-S. typhi 9L ,J* OHYHOV EHWZHHQ FKLOGUHQ ZKR KDG EHHQ YDFFLQDWHG PRUH WKDQ \HDUV SULRU WR WKH VWXG\ DQG FKLOGUHQ ZKR KDG QRW EHHQ YDFFLQDWHG ZLWK WKH 9L SRO\VDFFKDULGH W\SKRLG YDFFLQH

Methods

We conducted a descriptive, analytic, cross-sectional VWXG\ DW 7XPLQWLQJ 'LVWULFW 0DQDGR IURP -XQH WR 6HSWHPEHU 6XEMHFWV ZHUH LQFOXGHG E\ FRQVHFXWLYH VDPSOLQJ ,QFOXVLRQ FULWHULD IRU WKH YDFFLQDWHG JURXS ZHUH KHDOWK\ FKLOGUHQ DJHG WR \HDUV ZKR KDG EHHQ YDFFLQDWHG ZLWK WKH 9L

SRO\VDFFKDULGH W\SKRLG YDFFLQH PRUH WKDQ \HDUV SULRU WR WKH VWXG\ 3URRI RI YDFFLQDWLRQ ZDV REWDLQHG by subjects Kartu Menuju Sehat (KMS) or other PHGLFDO UHFRUGV &KLOGUHQ ZLWK SRRU QXWULWLRQDO VWDWXV ZHUH H[FOXGHG 7KH FRQWURO JURXS FRQVLVWHG RI FKLOGUHQ ZKR KDG QRW UHFHLYHG DQ\ W\SKRLG YDFFLQDWLRQ $OO FKLOGUHQ ZKR PHW WKH LQFOXVLRQ FULWHULD IRU WKH WZR JURXSV XQGHUZHQW VHUXP DQWLERG\ level examinations for anti-S. typhi 9L ,J* 6HUXP anti-S. typhi 9L ,J* OHYHOV ZHUH PHDVXUHG E\ enzyme- linked immunosorbnet assay (/,6$ PHWKRG 6HUXP DQWLERG\ OHYHO RI ! J P/ DQWL S. typhi 9L ,J* ZDV FRQVLGHUHG WR EH SURWHFWLYH DJDLQVW GLVHDVH 6XEMHFWV FKDUDFWHULVWLFV ZHUH DVVHVVHG E\ GHVFULSWLYH DQDO\VLV &RPSDULVRQV RI WKH WZR JURXSV ZHUH DQDO\]HG XVLQJ LQGHSHQGHQW 7 WHVW IRU PHDQ serum antibody levels and Chi-square test for the SURSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQLWERG\ OHYHOV

Results

'XULQJ WKH VWXG\ SHULRG VXEMHFWV ZHUH GLYLGHG LQWR WZR JURXSV FKLOGUHQ ZLWK D KLVWRU\ RI 9L SRO\VDFFKDULGH W\SKRLG YDFFLQDWLRQ PRUH WKDQ \HDUV SULRU WR RXU VWXG\ Q DQG FKLOGUHQ ZLWKRXW D SULRU KLVWRU\ RI W\SKRLG YDFFLQDWLRQ Q &KDUDFWHULVWLFV RI VXEMHFWV DUH VKRZQ LQ Table 1 ,QGHSHQGHQW 7 WHVW UHVXOWV RQ PHDQ DQWL-S. typhi9L DQWLERG\ OHYHOV EHWZHHQ WKH WZR JURXSV DUH VKRZQ in Table 2, ZKLOH &KL VTXDUH WHVW UHVXOWV WR FRPSDUH WKH SURSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQWL-S.

Table 1. 5WDLGEVU EJCTCEVGTKUVKEU

Variables6[RJQKF 8K XCEEKPCVKQP P 0Q V[RJQKF XCEEKPCVKQP P

)GPFGT /CNGU P

(GOCNGU P

/GCP CIG 5& [GCTU

/GCP $/+ 5& MI O2

Table 2. %QORCTKUQP QH CPVK S. typhi 8K +I) NGXGNU DGVYGGP VJG XCEEKPCVGF CPF WPXCEEKPCVGF ITQWRU

)TQWRU

CPVK S. typhi Vi IgG NGXGN zI O. /GCP 5& %+

2 XCNWG6[RJQKF 8K XCEEKPCVKQP 0.55 VQ 0Q V[RJQKF XCEEKPCVKQP VQ

typhi 9L DQWLERG\ OHYHOV EHWZHHQ WKH WZR JURXSV DUH VKRZQ LQ Table 3 7KH OHYHOV RI DQWL 6 W\SKL 9L ,J* LQ FKLOGUHQ ZKR KDG EHHQ YDFFLQDWHG ZHUH VLJQLILFDQWO\ KLJKHU FRPSDUHG WR WKRVH ZKR KDG QR YDFFLQDWLRQ Table2 7KH SURSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQWLERG\ OHYHOV ZDV QRW VWDWLVWLFDOO\ VLJQLILFDQW GLIIHUHQW EHWZHHQ WKH WZR JURXSV Table

WLRQ ZLWK WKH 9L SRO\VDFFKDULGH W\SKRLG YDFFLQH In our study, the mean anti-S. typhi Vi IgG level of the YDFFLQDWHG JURXS ZDV QRW LQ SURWHFWLYH UDQJH 6WXG\ conducted by Acosta et al VKRZHG VLPLOLDU UHVXOW WKURXJK GLIIHUHQW ZD\V $FRVWD et al studied the pro- tective efficacy of typhoid vaccination by calculating the incidence of typhoid fever (diagnosed clinicaly and VHURORJLFDO\ IURP SRVW YDFFLQDWHG VXEMHFWV 7KLV study found that in the second year after vaccination

Table 3. 2TQRQTVKQP QH EJKNFTGP YKVJ RTQVGEVKXG CPVK S. typhi 8K +I) NGXGNU zI O.

)TQWRU

2TQVGEVKXKV[ QH S. typhi 8K CPVKDQF[2TQVGEVKXG0QV RTQVGEVKXG P P

2 XCNWG6[RJQKF 8K XCEEKPCVKQP 0Q V[RJQKF XCEEKPCVKQP

Discussion

7KH 9L SRO\VDFFKDULGH VXEXQLW YDFFLQH LV D KRPR SRO\PHU RI JDODFWXURQLF DFLG ZKLFK LV H[WUDFWHG from the bacteria Salmonella typhi 7KLV YDFFLQH LV D 7 FHOO LQGHSHQGHQW YDFFLQH ZLWK ORQJ DQG UHSHWLWLYH HSLWRSHV ZKLFK DOORZ FURVVOLQNLQJ ZLWK immunoglobulin receptors located on the surface of% FHOOV ,PPXQRJOXEOLQ ELQGLQJ WR % FHOOV VXUIDFH UHFHSWRUV UHVXOW LQ % FHOOV DFWLYDWLRQ ZKLFK LQ WXUQ DOORZLQJ SUROLIHUDWLRQ DQG GLIIHUHQWLDWLRQ LQWR DQWLERG\ VHFUHWLQJ SODVPD FHOOV 7KH SULPDU\ LPPXQH response is induced at the time of first exposure to the DQWLJHQ $QWLERGLHV IRUPHG LQ WKH SULPDU\ LPPXQH UHVSRQVH DUH PRVWO\ ,J0 DQG ,J* JHQHUDOO\ DW ORZHU titers than that formed during a secondary immune UHVSRQVH $ VHFRQGDU\ LPPXQH UHVSRQVH LV PRUH adequately developed after exposure to the same antigen, hence, this type of immunological response LV H[SHFWHG IROORZLQJ ERRVWHU LPPXQL]DWLRQ $V VXFK WKH 9L SRO\VDFFKDULGH DV D 7 FHOO LQGHSHQGHQW DQWLJHQ DFWLYDWHV RQO\ D SULPDU\ LPPXQH UHVSRQVH ZLWKRXW a booster effect, so immunological memory is not GHYHORSHG Although the underlying immunological mecha- nism of response to the Vi polysaccharide typhoid YDFFLQH LV ZHOO NQRZQ WKH SURWHFWLYH HIILFDF\ RI WKLV vaccine may vary depending on typhoid endemicity of SDUWLFXODU JHRJUDSKLFDO UHJLRQ 3UHYLRXV VWXGLHV UHPDLQ inconclusive on the need for vaccination or revaccina-

the protective efficacy of the S. typhi Vi polysaccharide VXEXQLW YDFFLQH ZDV KLJK EXW LQ WKH WKLUG \HDU WKH HIILFDF\ GHFUHDVHG WR 2XU VWXG\ KDV VKRZQ that the drop in anti-S. typhi 9L ,J* OHYHO \HDUV RU PRUH after vaccination is responsible for the reduction in protective efficacy of S. typhi 9L VXEXQLW YDFFLQH ZKLFK VKRZQ E\ $FRVWD 6LPLODUO\ )URHVFKHOH et al LQ found that serum antibody levels induced by a single dose of Typhim Vi YDFFLQH GHFUHDVHG DIWHU \HDUV KHQFH UHYDFFLQDWLRQ HYHU\ \HDUV LV UHFRPPHQGHG 7KH PHDQ DQWL 9L ,J* OHYHO ZDV VLJQLILFDQWO\ higher in the vaccinated group than in the unvac- FLQDWHG JURXS 3 +RZHYHU DQWLERG\ OHYHOV LQ ERWK JURXSV ZHUH JHQHUDOO\ OHVV WKDQ WKH SURWHFWLYH OHYHO RI J P/ VXJJHVWLQJ D QHHG IRU W\SKRLG UHYDFFLQDWLRQ HYHU\ \HDUV DV UHFRPPHQGHG E\ SUHYLRXV VWXGLHV ,Q WKH XQYDFFLQDWHG FRQWURO JURXS RI FKLOGUHQ KDG SURWHFWLYH DQWLERGLHV DJDLQVW W\SKRLG 'HVSLWH WKH QHJDWLYH KLVWRU\ RI YDFFLQDWLRQV ZH suggest a role of environmental antigen exposure in developing antibodies among people at risk for VXFK H[SRVXUH +RZHYHU RXU UHVXOWV HPSKDVL]H WKDW vaccination should not be replaced by environmental DQWLJHQ H[SRVXUH 7KLV ILQGLQJ LV LQ FRQWUDVW ZLWK D study conducted in a highly endemic area in South$IULFD 7KH\ FRPSDUHG DQWL 9L DQWLERG\ OHYHOV EHWZHHQ FKLOGUHQ ZKR KDG UHFHLYHG WKH S. typhi Vi SRO\VDFFKDULGH VXEXQLW YDFFLQH \HDUV HDUOLHU DQG D FRQWURO JURXS ZKR KDG QRW UHFHLYHG WKH YDFFLQH

7KH\ IRXQG QR VLJQLILFDQW GLIIHUHQFH LQ DQWL 9L DQWLERG\ OHYHOV EHWZHHQ WKH WZR JURXSV )XUWKHUPRUH RI VXEMHFWV LQ HDFK JURXS KDG SURWHFWLYH DQWL 9L DQWLERG\ OHYHOV ! J P/ 6LPLODUO\ 7DFNHW et al VWXGLHG YROXQWHHUV LQ QRQ HQGHPLF DUHDV 1RUWK $PHULFD ZKR UHFHLYHG WKH 9L VXEXQLW YDFFLQH :LWK periodic checking, anti-Vi antibody levels in this group SHUVLVWHQWO\ LQFUHDVHG LQ YROXQWHHUV HYHQ PRQWKV DIWHU YDFFLQDWLRQ 7KHUHIRUH WKH\ FRQFOXGHG WKDW ZLWKRXW UHYDFFLQDWLRQ DQWL 9L DQWLERG\ OHYHOV LQFUHDVHG HYHQ DIWHU \HDUV )DFWRUV LQIOXHQFLQJ WKH SHUVLVWHQFH RI DQWLERG\ OHYHOV UHPDLQ XQFOHDU 3URSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQWL 9L DQWLERG\ OHYHOV LQ YDFFLQDWHG JURXS ZDV KLJKHU compared to unvaccinated group, although this GLIIHUHQFH ZDV QRW VWDWLVWLFDOO\ VLJQLILFDQW 3 7KHVH UHVXOWV HPSKDVL]H WKH QHHG IRU YDFFLQDWLRQ DQG UHYDFFLQDWLRQ LQ FKLOGUHQ LQ HQGHPLF DUHDV =KRX et al VKRZHG WKDW FKLOGUHQ ZKR ZHUH UHYDFFLQDWHG years after the first dose of S. typhi Vi polysaccharide subunit vaccine had significantly increased anti-Vi DQWLERG\ WLWHUV $ UHYLHZ E\ *X]PDQ et al stated that high-risk populations such as children in endemic areas, travelers and microbiology laboratory officials ZLOO EHQHILW IURP DQ HIIHFWLYH W\SKRLG YDFFLQDWLRQ $ OLPLWDWLRQ RI WKLV VWXG\ ZDV QRW REWDLQLQJ antibody levels to S.typhi DW PRUH WLPH SRLQWV ,QWHUYDO EHWZHHQ YDFFLQDWLRQ DQG WLPH RI DQWL 6 W\SKL ,J* levels measurement in vaccinated group also not FDOFXODWHG LQ WKLV VWXG\ $QRWKHU GUDZEDFN OLHV WR LWV FURVV VHFWLRQDO GHVLJQ ZKLFK PDNH XV XQDEOH to determine factors that contributed to a small SURSRUWLRQ RI FKLOGUHQ LQ ERWK JURXSV ZKLFK KDYH protective levels of immunity against S. typhi $OVR ZH ZHUH XQDEOH WR FRQWURO IDFWRUV LQGLUHFWO\ UHODWHG to typhoid antigen exposure, such as hygiene and VRFLRHFRQRPLF VWDWXV Although several studies recommend revaccina-WLRQ ZLWK WKH 9L SRO\VDFFKDULGH W\SKRLG YDFFLQH HYHU\ \HDUV RWKHU VWXGLHV VXJJHVW WKDW WKH QHHG IRU UHYDF- cination largely depends on factors that are not yet FOHDUO\ NQRZQ LQ D SDUWLFXODU UHJLRQ :H IRXQG WKDW WKH serum anti-S. typhi 9L ,J* OHYHO ZDV KLJKHU LQ FKLOGUHQ ZKR KDG UHFHLYHG W\SKRLG YDFFLQDWLRQV PRUH WKDQ \HDUV SULRU WR WKH VWXG\ WKDQ LQ FKLOGUHQ ZKR KDG QRW UHFHLYHG W\SKRLG YDFFLQDWLRQV 1HYHUWKHOHVV PHDQ DQWLERG\ WLWHUV LQ ERWK JURXSV ZHUH QRQ SURWHFWLYH DQG WKH SURSRUWLRQ RI FKLOGUHQ ZLWK SURWHFWLYH DQ-

WLERG\ OHYHOV ZDV QRW VLJQLILFDQWO\ GLIIHUHQW EHWZHHQ WKH JURXSV 7KHVH ILQGLQJV SURYLGH HYLGHQFH IRU KHDOWK practitioners to recommend typhoid vaccinations as ZHOO DV UHYDFFLQDWLRQV HYHU\ \HDUV LQ FKLOGUHQ RYHU years of age, especially those at higher risk for typhoid IHYHU LQIHFWLRQV

References

*X]PDQ &$ %RUVXW]N\ 6 *ULRW :HQN 0 0HWFDOIH ,& Pearman J, Collioud A, et al 9DFFLQHV DJDLQVW W\SKRLG IHYHU 9DFFLQH %KXWWD =$ .KDQ 0, 6RRIL 6% 2FKLDL 5/ 1HZ DGYDQFHV LQ W\SKRLG IHYHU YDFFLQDWLRQ VWUDWHJLHV $GY ([S 0HG %LRO 0DVNH\ $3 %DVQ\DW % 7KZDLWHV *( &DPSEHOO -, )DUUDU -- =LPPHUPDQ 0' (PHUJLQJ WUHQGV LQ HQWHULF IHYHU LQ 1HSDO FDVHV FRQILUPHG E\ EORRG FXOWXUH 7UDQV 5 6RF 7URS 0HG +\J 3XQGD 3ROLF 9 .UDOMHYLF .6 %UDGDULF 1 :DU DVVRFLDWHG cases of typhoid fever imported to Split-Dalmatia County &URDWLD 0LO 0HG &UXPS -$ /XE\ 63 0LQW] (' 7KH JOREDO EXUGHQ RI W\SKRLG IHYHU %XOO :RUOG +HDOWK 2UJDQ &UXPS -$ 5DP 3. *XSWD 6. 0LOOHU 0$ 0LQW] (' 3DUW , Analysis of data gaps pertaining to Salmonella enterica serotype7\SKL LQIHFWLRQ LQ ORZ DQG PHGLXP KXPDQ GHYHORSPHQW LQGH[ FRXQWULHV (SLGHPLRO ,QIHFW $JWLQL 0' 2FKLDL 5/ 6RHKDUQR 5 /HH +- 6XQGRUR - Hadinegoro SR, et al ,QWURGXFLQJ 9L SRO\VDFFKDULGH W\SKRLG fever vaccine to primary school children in North Jakarta,,QGRQHVLD YLD DQ H[LVWHQW VFKRRO EDVHG YDFFLQDWLRQ SODWIRUP 3XEOLF +HDOWK 6KDUPD 3 7DQHMD '. 7\SKRLG YDFFLQH D FDVH IRU LQFOXVLRQ LQ QDWLRQDO SURJUDP ,QGLDQ - 3XEOLF +HDOWK 2FKLDL 5/ $FRVWD &- $JWLQL 0 %KDWWDFKDU\D .6 %KXWWD =$ 'R &* et al 7KH XVH RI W\SKRLG YDFFLQHV LQ $VLD WKH '20, H[SHULHQFH &OLQ ,QIHFW 'LV V $FRVWD &- +RQJ +XL < 1LQJ : 4LRQ * 4XQ ' ;LDROHL 0 et al (IILFDF\ RI D ORFDOO\ SURGXFHG &KLQHVH 9L SRO\VDFFKDULGH W\SKRLG IHYHU YDFFLQH GXULQJ VL[ \HDUV RI IROORZ XS 9DFFLQH .OHGG\ .+ .OXJPDQ .3 +DQVIRUG &) %ORQGHDX & %RXYHUHW OH &DP 11 3HUVLVWHQFH RI DQWLERGLHV WR WKH 6DOPRQHOOD W\SKL Vi capsular polysaccharide vaccine in South African school FKLOGUHQ WHQ \HDUV DIWHU LPPXQL]DWLRQ 9DFFLQH

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