2013 Immunological Characteristics of Hyperreactive Malarial Splenomegaly

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Hindwi Puishing CorportionJourn o ropic MdicinVoum 2013, Artic ID 961051, 5 pgshttp://dx.doi.org/10.1155/2013/961051

Clinical StudyImmunological Characteristics of Hyperreactive MalarialSplenomegaly Syndrome in Sudanese Patients

Tayseer Alkadarou,1Ahmed Musa,1Abedelgader Alkadarou,2 Mohamed S. Mahfouz,3

Marita Troye-Blomberg,4Ahmed M. Elhassan,1 and Ibrahim M. Elhassan1,3

1 Institute of Endemic Diseases, University of Khartoum, Sudan2 Faculty of Medicine, University of Khartoum, Sudan3

Faculty of Medicine, Jazan University, P.O. Box 114, Jazan, Saudi Arabia4 Department of Immunology, Te Wenner-Gren Institute, Stockholm University, Sweden

Corrspondnc shoud ddrssd to Irhim M. Ehssn; [email protected]

Rcivd 2 Dcmr 2012; Accptd 8 Frury 2013

Acdmic Editor: Adity Prsd Dsh

Copyright ysr Akdrou t . Tis is n opn ccss rtic distriutd undr th Crtiv Commons AttriutionLicns, which prmits unrstrictd us, distriution, nd rproduction in ny mdium, providd th origin work is proprycitd.

Hyprrctiv Mri Spnomgy (HMS) is dfnd s mssiv nrgmnt o th spn rsuting rom norm immunrsponss r rptd xposur to th mri prsits. Tis study ws crrid out in Khrtoum, Sudn. Sudn is considrd

to on o th countris whr HMS is quit prvnt. T ojctiv o th study ws to dtrmin th incidnc o HMS inptints who rportd to th Omdurmn ropic Disss Hospit (OMDH) in Sudn nd to invstigt th sic ortorynd immunoogic chrctristics o this condition in ths ptints. A cross-sction study ws crrid out in OMDH, nd ptints with nrgd spns wr incudd in th study. Tirty-on out o 335 (9.3%) ptints wr dignosd s hving th HMScondition using intrntion critri or HMS dignosis. T mn srum immunogouin M (IgM) vs in HMS ptint groupswr 14.3 5 g/L, nd this ws signifcnty highr comprd with gogrphicy mtchd contros ( < 0.001). ImmunogouinG (IgG) C nticircumsporozoit (CSP) ntiody vs wr highr in th HMS ptints though th dirnc ws not sttisticysignifcnt, whn comprd with group o ptints with mid mri. In comprison with nv Europn contros, oth thHMS nd th mid mri groups hd signifcnty highr ntimri ntiody vs < 0.001 nd < 0.01, rspctivy.Psm vs o intrukin 10 (IL10) nd intrron gmm (IFN) wr signifcnty incrsd in th HMS ptints comprdwith th hthy contro donors ( < 0.05 nd < 0.01) or IL10 nd IFN, rspctivy. T fndings o this study suggst thtHMS is on o th signifcnt cuss o tropic spnomgy in Sudn. HMS is ssocitd with signifcnt vtions o circutingIgM nd ntimri IgG ntiodis s w s IL10 nd IFN.

1. Introduction

Hyprrctiv Mri Spnomgy (HMS) is chrctr-izd y mssiv nrgmnt o th spn in th tropics. Tcondition is prvnt in crtin mrious rgions o th OdWord, miny in Aric [15].

HMS sms to ssocitd with high mortity;howvr, th ntur history o HMS is not w documntd.A 5-yr-mortity rt o 50% hs n rportd in Ugndnd Nw Guin [6]. A mortity rt o 85% hs n doc-umntd in hospitizd ptints with gross spnomgy.

Whthr HMS is rsponsi or this high mortity is cttht sti nds to stishd [6].

Clinical Features. Symptoms o spnomgy consist primr-iy o uppr qudrnt pin with or without signs o hypr-spnism dominting th cinic prsnttion o HMS. Eryin th syndrom, th pin my pisodic nd xcrtdy physic ctivity, which ovr tim progrsss in intn-sity nd coms prsistnt nd diitting. Hmoyticpisods ssocitd with cut ri inss or prgnncycn prcipitt th cours o HMS nd, on occsion,
http://dx.doi.org/10.1155/2013/961051http://dx.doi.org/10.1155/2013/961051


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ssocitd with suddn dth. Physic xmintion usuyrvs mssiv spnomgy o th spn on xtndingcross th midin to th right sid o th domn ordownwrd to th iic oss. T spn is gnry frmnd nontndr with prominnt notch nd rgur contour.Hptomgy, most commony o th o, on coxists

nd tnds to pr th siz o th spn. T pthognsiso HMS is sti not uy undrstood, yt thr sms to grmnt consnsus on th hypothsis postutd rir yFkun nd Zigr tht HMS pthognsis rsuts rom IgMovrproduction du to B ymphocyts stimution y mrintign/mitogn [7, 8] s ing th sis or th dvopmnto HMS.

Howvr, th occurrnc o HMS in tri nd miycustrs suggsts host gntic ctors invovmnt in thcontro o th IgM ovrproduction sn in ths ptints.Hyprrctiv mri spnomgy is ony ound in mrindmic rs [9]. Mri in Sudn is ndmic nd chr-ctrizd y sson trnsmission in most prts o thcountry [10]. Currnty thr is no vi inormtion onth prvnc nd incidnc o HMS in Sudn, prt romrcnty puishd dt in th strn prt o th countrywhich indictd tht HMS is mjor cus o spnomgyin this prt. In this rs HMS constituts 11% o th toto spnomgy css [11]. Tis study ims to ucidt thprvnc nd immunoogic chrctristics o HMS inSudns ptints.

T unusu immunoogic turs o HMS, sdscrid rir, might contriut to our undrstnding oth mchnisms invovd in pthognicity nd immunity tomri.

2. Methods

2.1. Study Area. Tis study ws crrid out in th Ommdur-mn ropic Disss Hospit (ODH), Khrtoum, Sudn,whr ptints rom dirnt rgions o Sudn r rrrd to.

2.2. Study Design. A cross-sction study ws crrid outrom Jnury 2004 to Dcmr 2006. A ptints (330ptints) prsntd to th outptint cinic with nrgspn wr incudd in th study.

Ethic pprov o this study ws otind rom ththic committ t th Institut o Endmic Disss,Univrsity o Khrtoum. Inormd consnt ws otind

rom duts nd in cs o chidrn rom thir prnts orgurdins. Ptints with svr disss wr xcudd romthis study.

T dignosis o HMS ws sd miny on th stndrdcritri or dignosis o HMS [12] which incudd physicxmintion such s mssiv spnomgy nd xcusiono othr common cuss o hug spn, tht is, historyo hptitis or coho us, xposur to schistosomisisor ishmnisis, miy history o hmogoinopthisor cinic vidnc o vr, jundic, ymphdnopthy,hptomgy, nd port hyprtnsion. Finy, th ormincudd history o mri in trms o numr o ttcksduring th yr, st cinic ttck, nd trtmnt rcivd

tht ws compid or ch ptint. ot nd dirntiwhit c counts wr crrid out or ptints to xcudukmi. Urin nd stoo smps wr xmind to xcudschistosomisis rucosis using th Wid tst kit (HnsrdDignostic Limitd, UK).

Furthrmor, th immunoogic prmtrs in st-

ishd HMS wr msurd nd comprd with mid mriptints nd contro groups.Sr rom 33 ptints with prsitoogicy confrmd

mid mri rom highy ndmic rs in cntr Sudnwr usd s positiv contros or immunoogic ssys.

Ptints wr intrviwd, nd u cinic history wsotind using spciy dsignd orms which incudd thnm, sx, g, tri, nd ddrss.

A css with HMSwr trtd with choroquin300 mgwky, in ccordnc with oc trtmnt protoco, nd thywr instructd to rport to th study tm t th hospit oroowup onc month or 3 months.

2.3. Blood Sampling. n mL o priphr ood wscoctd rom ch ptint y vnipunctur into EDA

vcutinrs; ood smps wr coctd into pin stricontinrs to sprt srum within 12 h o coction. Psmsmps wr stord rozn t 20C. T pckd rd oodcs wr trnsrrd into stri tus nd stord t 40Cor DNA xtrction.

2.4. Parasitological Examination. Tick nd thin fms wrprprd rom study sujcts, stind with Gimss ndxmind undr microscop. Fims wr considrd ngtivr xmintion o 300 oi fds without dtction omri prsits.

n mL o priphr ood ws coctd rom chptint y vnipunctur into EDA vcutinrs; ood sm-ps wr coctd into pin stri continrs to sprtsrum within 12 h o coction. Psm smps wr stordrozn t 20C. T pckd rd ood cs wr trnsrrdinto stri tus nd stord t 40C or DNA xtrction.

2.5. Polymerase Chain Reaction (PCR). PCR nysis ws cr-rid out on smps coctd rom ptints or dtctiono mri prsits; th primrs spcifc or th poymorphicrgions ock 2 o mrozoit surc protin 1 (MSP1) ndock 3 o (MSP2) wr dsignd nd dscrid prviousy.T two gns wr mpifd using nstd PCR. An initimpifction o th outr rgions o th two gns wsoowd y nstd PCR with ic miy spcifc primrpirs [13].

2.6. Haemoglobin Level. Hmogoin concntrtion wsstimtd y Drkins mthod [14].

2.7. Immunological Methods. Msurmnt o tot humnIgM: tot (IgM) ws msurd using th MININEPHMHumn IgM Kit Binding Sit Limitd, UK. Srum smpsrom 31 hthy Sudns donors wr incudd s controsin th nysis.


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2.8. Circumsporozoite (CSP) Peptide ELISA. A synthtic pp-tid drivd rom dirnt rgions o th circumsporozoitprotin ws usd in this study. Tis ntign ws synthsizdccording to protoco stishd y [15, 16]. T pptid wsconjugtd with ovin srum umin (BSA). T ELISAtsts wr crrid out using th stndrd mthod dscrid

swhr [17].Cuto ws dtrmind s th mn pus 2 stndrddvitions o th optic dnsity (OD) vus otind withsr rom 10 Europn donors with no history o mrixposur. Tirty-thr sr rom prsitoogicy confrmdP. falciparum inctd ptints rom highy ndmicmrir wr usd s positiv contros.

Dtrmintion o th psm vs o intrukin 10(IL10) nd gmm intrron (IFN): psm vs o IFNnd IL10 cytokins wr msurd in th psm smpscoctd rom HMS ptints nd hthy contro donors ydou sndwich ELISA using commrciy vi R & Dsystm Eis kits (Grmny).

2.9. reatment. A ptints with HMS wr trtd withchoroquin 300 mg wky in ccordnc with th stndrdtrtmnt protoco nd wr instructd to rport to th studytm t th hth cntrs or oowup onc month or 3conscutiv months.

2.10. Statistical Analysis. Dt ntris wr prormd usingth Exc progrm. T PASW 18.02 sowr progrmmws usd or dt nysis. Frquncy distriutions wrotind, nd dscriptiv sttistics wr ccutd, incudingcntr tndncis, stndrd dvitions, nd 95% confdncintrvs. For compring th two groups (mri ptints

vrsus contro ptints), Studnts t-tst ws usd to vutwhthr thr ws signifcnt dirnc in th two studidgroups in thir immunoogic prmtrs. A sttistic tstswr two-sidd; v o < 0.05 ws usd to indictsttistic signifcnc.

3. Results

3.1. HMS Patients. T g o ptints rngd rom 10 to 70yrs; mn g ws (26.3 14.3) yrs. During th studypriod, 31 out o 335 (9.3%) ptints wr dignosd withHMS ptints. T cinic, hmtoogic, nd immunoog-

ic chrctristics o th ptints r shown in 1.

Tmn spn siz ws 12.7 4.65. T mn ivr siz ws2.02.67. T mn H v ws 10.32.5. T WBC countws 3050 1062 ( 1).

T ptints with nrgd spns wr oowd up or 3months. Out o 33 HMS css, 21 (70%) o thm comptdth cinic oow-up priod up to dy 90. In 14 ptints(66%), thspns wr impp t thnd o th3 months.

3.2. Parasitological Results. No mri prsits wrdtctd in ny o th HMS ptints group using microscopicxmintion. Howvr, poymrs chin rction nysisindictd tht on HMS cs ws hrouring ow grd

able 1: Cinic hmtoogic nd immunoogic chrctristicoHMS ptints.

M-m rtio 3 : 2

Mn o g SD (rng) (yrs)26.3 14.3

(1070)

Mn spn siz SD (cm) 12.7 4.65

Mn ivr siz SD (cm) 2.0 2.67

Mn hmogoin concntrtions SD (g/dL) 10.3 2.52

Mn o whit ood cs SD (rng) (L) 3050 1062

Mn o srum concntrtion o totIgM SD (g/L)

14.3 5

Mn v o nti-CSP ntiody vs (OD) 0.92 0.31

able 2: T psmvo IFN nd IL-10concntrtions (pg/mL)in hthy contros nd HMS ptints (confdnc intrv o mnv 95%).

Mn SD95% CI or

th mnSignifcnc

IFN

Contro 60 8.5 57.063.0P< 0.05

HMS 75 14.2 70.080.0

IL10

Contro 28 19.8 21.035.0P< 0.01

HMS 42 25.5 35.053.0

ciprum prsitmi. A mid mri ptints wrpositiv or P. falciparum.

3.3. Immunological Results

3.3.1. otal IgM Concentration. T mn srum IgM vswr comprd twn HMS ptints nd 33 (g, sx, ndgogrphicy mtchd) hthy dut contros. T mnIgM v o th contro ws 0.90.6 g/L. T mn IgM vin th HMS ptints group ws 14.3 5 g/L, fnding whichws signifcnty highr s comprd to th hthy contro( < 0.001).

3.3.2. Anti-CSP Antibodies. T mn IgG nti-CSP ntiodyvs wr 0.92 0.31, 0.76 0.4, nd 0.34 0.14 in HMS,

mid mri nd ngtiv contros, rspctivy.T vs o nti-CSP ntiody ws signifcnty highr( < 0.001 nd < 0.05) in HMS css nd in mid mriptints, rspctivy, comprd with ngtiv contro. Nosignifcnt dirnc in th IgG nti-CSP ntiody vs wssn twn HMS nd th mri ptint groups ( >0.05).

3.3.3.Te PlasmaLevels of IFN and IL10 in theStudy Subjects.T psm vs o IL10 nd IFN r summrizd in 2. T mn psm vs o oth IL-10 nd IFN wrsignifcnty highr in th HMS ptints, comprd with thhthy contro donors, < 0.05 nd < 0.01, rspctivy.


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4. Discussion

In th prsnt study, 31 out o 335 spnomgy ptints(9.3%) prsntd with HMS conditions. Tis indicts thtHMS is signifcnt cus o tropic spnomgy in Sudn.

In thisstudy, th IgG nti-CSP ntiody vs wr oundto sighty highr (though not sttisticy signifcnt)in th HMS ptints comprd with mid mri ptints(>0.05), whrs ntimri IgG ntiody vs wr sig-nifcnty incrsd in oth HMS nd mid mri ptintscomprd with mri ngtiv Europn contros (

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2013 Immunological Characteristics of Hyperreactive Malarial Splenomegaly