2009 Cerebral Malaria Nature Neurol Mishra & Newton

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nature reviews | neurology voume 5 | aPri 2009 | 189

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ipat Gnal Hoptal,roukla, Oa, inda(SK Misha). KeMri/

wllcom TutCollaboat Pogam,Cnt o GogaphcalMdcn (Coat), Kl,Knya (CrJC nwt).

Copondnc:CrJC Nton,Nuocnc Unt,inttut o ChldHalth, Unty Collg London, Thwolon Cnt,Mcklnbugh squa,London wC1N 2AP, UK [email protected]

Diasis ad maamt f th icacmpicatis f facipam maaiaSaroj K. Mishra and Charles R. J. C. Newton

Abstact | Malaa a majo publc halth poblm n th dlopng old ong to t hgh at o mobdty

and motalty. O all th malaal paat that nct human, Plasmodium falciparum mot commonly

aocatd th nuologcal complcaton, hch mant a agtaton, pycho, zu, mpad

concoun and coma (cbal malaa). Cbal malaa th mot nuologcal complcaton;

th condton aocatd th motalty o 15–20%, and a ubtantal popoton o nddual th th

condton dlop nuocognt qula. in th r, dcb th aou nuologcal complcaton

ncountd n malaa, dcu th undlyng pathogn, and outln cunt managmnt tatg o

th complcaton. Futhmo, dcu th ol o adjunct thap n mpong outcom.

Mha, s. K. & Nton, C. r. J. C. Nat. Rev. Neurol. 5, 189–198 (2009); do:10.1038/nnuol.2009.23

Introduction

m y c -dc ;h d cgy w c f pp gg g f ch .th Plasmodium falciparum p pb f h gc cpc cdh , hgh P. vivax c z ch-d, d cd h c bh chdd d.

i 2002, d 2.2 b dd xpd P. falciparum -dc , h515 cc pd d 1 dh.1

o 70% f h fc ccd chd g b-sh afc, hgh P. falciparum c fch y g. th gc f f cd z, pych, g, pdcc d c; h f hhk f cb .2–4 i -dc, gc f fd y hf f chd dd hp h fcp .5 i h dd dp d, hpp f p h dp cb f b chd d d.6 Cb cc 2.4% f h fcp ,7 d h b dcbd; h, h h -

gc cpc f fcp h cdy .i h r, dcb h gc f-

f fcp d d chd, dh phg d g f h cpc,h pc fc h bd d hdjc hp. i dd, hghgh f f ch h h f pg c.

Diagnosis

th dg f fcp hd b c-dd y p h h fb hgc yp d h pd hgh dc h p 3 h. occc f pp g p, ccd f bd f. th dgc h ccpc x f dbd , b pd ch h -chgphc f P. falciparum hd-chp 2 d c dhydg b.8 Py ch c g f p -

g rna Dna h ccpy,b xp d d pd f h p d.

i -dc , fcp dg f xc, hch h g bd 8–12 h qd bf h dg- c b d . my fc d bcpc c h yp f gc yp dg cd h , d h p- gh b cd c. i c dy f m, 24% f h chd h ffd h c- f cb bf dh hd dc p f c f h c.9 th

pc f phy (Fg 1)10

hy cc f h dghd p hypc hphgc f f cb f h h phg. a bpc b pfd xcd h cf h cphphy, hgh h c b dpcy11 d c p , p-by f z.12 ngg ph cb gh d b -g, cc fc, d hyp h h (Fg 2);13–15 h, f h f dgc f cb .

Cmpti itsts

Th autho dclad no comptng ntt.

© 2009 Macmillan Publishers Limited. All rights reserved

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Pathogenesis

th q chcc f cd by P. falciparum cpd h h h pc f p- h q f fcd yhcy h f g, pcy h b. thf hgh c y f h cpc f , pcy h gc f.

af h pz jcd h hbd by h f Anopheles q, h p- g hgh ypc hpc g. thfcd hpcy b, d h z,

Key points

Nuologcal complcaton a common n alcpaum malaa; cbal malaa■

th mot and aocatd th almot all nuocognt qula

and dath om nuologcal complcaton

Th pathogn o th nuologcal complcaton multactoal, th■

qutaton o nctd ythocyt n th ban th pobabl cau o mot

nuologcal complcaton

subtl dct uch a cognt mpamnt a otn undtctd, and ■

data a aalabl on th ncdnc o and thaputc opton to pnt

ban damag

Th mantay o malaa thapy pantal qundn, qunn o atunat;■

atunat th tatmnt o choc h aalabl

Adjunct thap mght hlp to mpo outcom, but a yt non ha■

unquocally bn hon to b bncal

hch h yhcy. i h 48 h fcyc f z h h yhcy h pdc hcc yp f . i h g, fcdyhcy dh h dh c f h , p gh f h p y hypxc d d dc h p. thcydhc dd by p cdd by h

var g f h p. th p xpd h fc f fcd yhcy, h hy c p f ch gd pgd h dh. i h g, h p bcy c, d c gc d pdcc bc gycy. ifcd yhcy qd y g f h bdy, h hb bg pfy gd, fd by hh, d k.16 th dg f q cb cd by bdg f dh fcd yh-cy h fcd yhcy (gg) fcd yhcy (g), by p-dd cpg.

th q f fcd yhcy dccc f, pc h ggd by dcd dfby f fcd fcdyhcy. t c ky cc, dc f chc dg x d h cc g pdy. H, cc dc ghcc h ppy f bc b h b,ggd by hypgyc h pcf cd b b h z d f.

P. falciparum c f bh pfy d -fy cyk, b h f hc d phg c. f (pfy) c fc (tnF), -

k (i)-6 d -fy i–10 cd p h cb cpd hh h . s pyph hTNF g p cd h cd k f cb , gc q d dh.17 i p f v d, f i-6, i-10d tnF d p h g d, b d (b ) p h cb , hch ggh h cyk d h phg f , b c per se.18

rc d pd c bd f i-1 cp g d

chd.19

ah dy ggdh p f dcb p 10 (iP-10), hb tnF cp tnF-r2 d b F p- gh b p bk f cb y d y.20 By c, hgh f -c dh gh fc pc gdh cb . P- y f b f p h cb h g-gd cd c pdc f tnF, i-1 dfg gh fc b .21 H,pdc f g f h cyk dd c h p q.

Figure 1 | Malaal tnopathy. Photogaph o th tna npatnt th malaa, hch ho xudat (aohad),hmohag (thck ao) and chang n th colo o th blood l (thn ao). Pmon obtand omNck Ba, royal Lpool Unty Hoptal, Lpool,UK and T Taylo, Blanty Malaa Pojct, Qunelzabth Cntal Hoptal, Blanty, Mala.





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nc xd (no) h b ggd ky ffc- f tnF h phg f . Cykpg dcb no yh b dhc d c h pdc f no, hch dff h b .22 icd no cy ghchg bd f d dc g pk, dg xcxcy. no ky dc h f

cc pdy d by, bc h h-d c c y dff c h bd–bb f h fc.

G h p gy cfd h - c pc, j q gdg h ph-g f cb : h d h p c dyfc?23 th bd–b b b pd p h cb ,17 d h h h gc f f .24 P y f h b f d h c-b h h dpd c dhc c h dp f c jc p(z ccd 1, ccd d c), pc-

y h c fcd yhcy.21 thpc gh b ffc b pcc pcp z.

B g cy gg p h cb (Fg 2).13–15 th -g cd h gc d, hghcyxc d p.14,15 th bg pbby bb cd bd h cc f q f hfcd yhcy d/ c cbbd f, pcy p , f dz. rd c p cc ch-d h cb , d chd dp

c hyp, hch gh b c-d h dh gc q.25 ichyp c d.

P- x p h c-b d q f fcdyhcy p f h b. th b f—dc f fk h d,b c chd. exyhcyc h-z ( pdc f hgb b by p) fd d cb ,26 hch g-g h p f qd, fcd yhcygh d fy pc h dd b cp. th fdg

cy d,27

d gh fc dffcb d d chd. th cb f c- cggg, c c g d hcd c pby h b a d.28 i dd, phgc f h,29 c f h bd cg ccd30 d p-dcdcpg f P. falciparum-fcd yhcy31 hb ppd. app f dh c cd by P. falciparum-fcd yhcy f chd hb pd ex vivo d, b c c- h gc cpc q fd.32 app h b h b f

d dyg h cb , b h fqcy f g f c cp 3, k f pp, gfcy hgh h c ddh .33

Neurological complications of malaria

th gc cpc f fcp

c f c hdch, by, g,z, pych d pd cc (fcf dp c). my f h f ccc h p dff dg hc f h .

Cba maaia

Cb h f f dff cphphy h bc cd, ccy h fc g.

Definition

th wHo df cb b c

(b cz pf ) p h h pc f P. falciparum x ph b dd, f h c f cph-phy h b xcdd. th df dpdf ch pp, d y p p h p f cc. th phd b d h p hpy dc gcy, dp gh wHo c.4

i hp, hypgyc d c bcg c b y xcdd, b h xc f h c, ch cph d bc

a b

Figure 2 | FLAir mag o th ban o a patnt th cbal malaa. a | Lo o ulc and naong o th ntcl (ban llng), th hypntnty n thmoal cntum along th abnomal gnal n th plnum o th copucalloum (ao). b | On k at th ont o lln, th mag ho

dnng o th ulc and ntcl, th oluton o hypntnt, xcpt oth lon n th plnum o th copu calloum (ao). Abbaton: FLAir,lud-attntuatd non coy. Pmon obtand om th Amcansocty o Nuoadology © Codolan Y. s. et al. AJNR Am. J. Neuroradiol. 19,871–874 (1998).





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c, c b pbc, pcy -dc h fc d. sz cp h f cc, h h f f bcc z pc .

Clinical presentation

a p h cb p h

f, g d/ ch. s p gh hhdch g. ad gh bp f h , gh dp y pd f dy. sg f by, pychc bh c b h ff cb .3,4 a hy f d bdf hd b gh p h ph h yp.

i chd h cb , c y d-p pdy, d f f z. i d, cdp gdy d y ccy cdh z.2 ad 15–20% f d h cb h z, cpd h 80% f chd.

m z b gzd cc b-, b eeG df fc g y p.ecc dchg h cc f h b cc f c.34–36

nck ff ccy cd,37 bh g f g (f xp, Kg g) c xpc. Phphb . C bd d, b chd. Cg ph py pp-b , cbbbg, hz d c yg, d xh p ccy bd.3 Ddf cjg gz ypcy p, b ppy

b cy chd h d. ab ccphc d cbfx cc chd h dp c.38

ngc x f h b y g-g yc pp dyfc,3 hgh c d d jk, hch y cd h cd, c b dpd. ak p c c b p c. B x p fx c p. Fc dfc ch hpd d c c cc.3

Dcc dcb pg c chd h d h cb . th p-

g c cc c h hypgyc, bf dc d c p. Gzdx p cd h phc pd d- f h y, pg, d pd f bhg h b dyk h b bd.expyd g c b bd, f dgccc. a p fx, bx bk j jk gh b p. th gg fx y pd,xcp dp c.

P h cb f xhb chg d hyh, h dffcy pg xcp. P gh h dzd c k,

xpc b. tk d yg c dg cy f c.

Sizs

i afc chd dd hp h z, c c.6 th z c b fb—hgh hf cc h h chd fb—d

y c hy p, fc pgd.39 Cc z cd h -c p. i eeG cdg f y f-qcy, h bckgd yy, b pp, c dchg, cd h dc.34,35 i d, z cc p hcb p f p gcyd ( b). s ppc d, hgh p c c. By c, ppc c chd, d y h cx f cb . eppy h b dcd f cy f cb afc chd.40 H, dd ch

b qd d h cc d cgphcf, phg d c f h q.

oth ica fats

Pychc f, ch hc, pych-, fg, d d , c cc p-g yp dg cy p h .th yp c b cd by dg; pc, chq, q d fq.

ncitiv sqa

ngc q f cb chd h d. th pc f

gc dfc b 6% d 29% h f hp dchg.41 i chd, gcb gh b (f xp, pych- x), gh p pdy h (fxp, cc bd ph), gh pf pgd pd (f xp, hp xpyd yd).42,43

i d, q c, d g f3–10% pc.44–46 i id, 10% f d hdgc q dchg, cdg pych(4%), cb x (3%), d xpyd gd-y hpg.45 th dph d d f c dp c dpd k fc f

gc q.sb dfc (f xp, cg dffc,gg d bh pb) cgy cg-zd, d h b dcd 24% f chd fcy f cb .47,48 th pc f hp d f h f f k, bc f ck f g- f-pd h pychgc x.

i dy f 187 ugd chd, 26% f chdh cb d 13% h cpcd hd cg dfc 2-y f-p x, cpd h 8% f





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hhy chd. th dfc chd h cb py h f (18% c-b 3% c).49 i chd h cb, hgh f tnF pdc h b cd h bq gc d cgbdy.50

Pstmaaia sdmst gc yd h b bd dgh cy f , h h ph cd. Cb x h b pd pcg f cb , h p - f h x pd f h. 51,52 a f-g ‘p gc yd’ hc f c cf , c pych, g-zd c d/ b 0.1% f p f .53 th cd cdh h f fq.

Management of cerebral malaria

P h pcd cb hd bfd h b b hh c fcy.4 idd p d f dg, g hd b dcd d y cg d ppp g f ccpc ch hypgyc, fd d c-y bc, c, , cd, d d py p.

Atimaaia ds

a dg h y hqcy dc y p h .th cchd (q d qd) d

cpd cy d, d bcg h dg f chc ( b). a dgd cdd b pcd bchd pdy.54 Bh h cchd d y cbd h h dg h h d f hpy ( h c f q)d p c (g d Bx 1).

Q h hpc d bc y k p h g f h yhcyc cyc.i c dc hypgyc by pg c-. oh cpc ch dzz d cch- bc d h p g cc.Q c hyp f g pdy h -

, d c pz (dcd by pg f h Qt ).4 Qd d pfc q h us.55

th —h, h d -— h d f Ch dg qgh.th dg h pdy cg d p - cpd b; hy k h gf h p h h yhcy, d k hgcy. i g, p-b, dzd f a d h , gf-cy dcd y by 34.7% (P = 0.0002, 95% Ci18.5–47.6%) cpd h q,56 d dy

afc chd cy dy.57 th wHo cd h dg f chc h f .54 th c-

pd cd y c, b h us c b d g dg f .55 a d cb dd h c , d h f c yc d ffc.

Maamt f th cmpicatis

th gc cpc f fcp f cd h dyfc f h g dy, h ffc ch , hypgyc,c f, hpc p, d cgdd. th pc f h h cpc

Box 1 | Antmalaal dug ud n th tatmnt o cbal malaa

ga picips

Admnt antmalaal dug pantally o at lat 48 h; that admnt■

oally a oon a patnt can allo

Admnt a loadng do■

Total duaton o thapy dpnd on ntty o paat, but uually 7 day■

Atmisii divativs

Atunat: to 2.4 mg/kg do gn ntanouly 12 h apat on day 1,■

thn 2.4 mg/kg daly o 6 day, gn oally patnt can allo. Admnt

ntamuculaly o ctally no ntanou acc

Atmth: 3.2 mg/kg ntamucula loadng do, thn 1.6 mg/kg p day ■

o 6 day, gn oally patnt can allo. Abopton mght b atc npatnt n hock

Atth: 150 mg onc a day by dp ntamucula njcton o 3 concut■

day (adult)

shot-duaton a tmnn (3 day): ollod th mloqun o■

uladoxn–pymthamn compound to pnt cudcnc

Qii

Dlut qunn dhydochlod th nomal o dxto aln and nud o■4 h (pably a yng o nuon pump)

Loadng do: 20 mg/kg body ght (alt) nud o 4 h■

Mantnanc do: 10 mg/kg body ght nud y 8 h untl oal■

admntaton pobl

Qiidi cat

Loadng do: 6.25 mg/kg ba (=10 mg/kg alt) nud ntanouly ■

o 1–2 h, thn contnuou nuon o 0.0125 mg/kg/mn ba

(=0.02 mg/kg/mn alt). i contnuou nuon mpactcal, u 15 mg/kg

ba (=24 mg/kg alt) loadng do nud ntanouly o 4 h, thn7.5 mg/kg ba (=12 mg/kg alt) nud o 4 h y 8 h, tatng 8 h at

loadng do

Mantan blood qundn ll n ang o 3–8 mg/l. At lat 24 h o qundn■

gluconat nuon a commndd (o 3 ntmttnt do); onc paatdnty <1% and th patnt can tak oal mdcaton, patnt can complt

tatmnt cou th 10 mg/kg (alt) gn oally y 8 h

intal (ncludng loadng) do o pantal qunn o qundn nd not■

b ducd n nddual th nal alu. i nal alu pt o thpatnt do not mpo, duc mantnanc doag by 25–33% on thd

tatmnt day

Obtan htoy o cnt u o dug that mght polong QT ntal (.g.■

qunn o mloqun) bo dcdng loadng do





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fc h p’ c.58 Bc fc- c chd h p h ff ,59 d ppp cb hpy hd b dd.

Hypgyc cc 3% f d h fcp ,56 d pcy c chd, pg , d p q

hpy. Hypgyc c b cd h d-g cc, gzd z, x p-g, hck d c, b f cc g d, d bd gc hd, hf, bd g . Hypgyc pd dd hpy,60,61 hgh hypchypgyc c h q hpy pd g-cg g.62

ac z f d by bzdz-p,63–65 hgh h dg gh b ffc h h cd, dg γ-byc cd cp.66 Pgd

z c y b d h phbb67 phy.67,68

th fd bc cc . Chdh h cd f hypc d qfd, b c x h pyp d f fd-pc hpy. ad cdp p d/ py d, d

fd gh, hf, d b cd. i ph cb h h d c p- h cb pf p d b p-zd, hgh f fd d hpc h b cy bhd. Pbf p d hyp cc fqy , b y cd h cc f p c.

Bd f d cc ;h f bd fd d h pdy f d dff b chd d d. iafc chd, fh h bd (10–20 /kg)

Table 1 | randomzd tal o ant-nlammatoy and antoxdant thap n malaa th nuologcal complcaton

rfc Dsi ad ima Patits otcms

Corticosteroids

wall et al. (1982)44

rDPCT o dxamthaon (1.5–2.0 mg/kgo 48 h)

100 Tha chldn and adult thcbal malaa

Dxamthaon polongd DoC (63 h 47 h n placbogoup); complcaton n 26% o dxamthaon goupu 11% o placbo goup

Homan et al. (1988)71

rDPCT o dxamthaon (11.4 mg/kgp 48 h)

38 indonan chldn and adultth mpad concoun

No gnfcant dnc n FCT, PCT and DoC

rampngan(1991)72

randomzd tal o dxamthaon (4.5 mg/kgp 72 h) u hpan (300 U/kgntamuculaly daly o 3 day) u nth

62 indonan chldn and adultth mpad concoun

No gnfcant dnc btn goup n motalty onuologcal qula

Immunomodulatory therapy

Taylo et al.

(2002)81

rDPCT o HiG pufd om plama o localm-mmun blood dono (400 mg/kg by ntanou nuon o 3 h) u placbo(albumn and uco nuon)

31 Malaan chldn thcbal malaa

No dnc n motalty: 5 o 16 patnt gn HiGdd compad th 1 o 15 cng placbo; nodnc n DoC, FCT o PCT

an Hnboket al. (1996)80

rDPCT o monoclonal antbody (B-C7)agant TNF

610 Gamban chldn thcbal malaa

No dnc n motalty; nuologcal qula n 15(6.8%) o uo n B-C7 goup compad th 5 (2.2%)uo n th placbo goup (adjutd odd ato 3.35,95% Ci 1.08–10.4)

Iron-chelation therapy

Goduk et al. (1992)73

rDPCT o doxamn (100 mg/kg p day nud o a total o 72 h)

83 Zamban chldn (<6 yaold) th cbal malaa

shot DoC n doxamn goup (20 h) u nplacbo goup (43 h); apd PCT n doxamn goup

Thuma et al. (1998)74

rDPCT o doxamn (100 mg/kg p day nud o a total o 72 h)

352 Zamban chldn (<6 yaold) th cbal

No gnfcant ct on motalty o DoC

Mohanty et al. (2002)99

rDPCT o oal dpon (75 mg/kg) 45 indan patnt Dpon mpod FCT, PCT and DoC

Pentoxifylline

D P et al. (1995)78

rDPCT o pntoxylln (10 mg/kgcontnuou nuon)

56 Buundan chldn thcbal malaa

shot mdan DoC n pntoxylln goup (6 46 h);tnd toad ducd motalty n pntoxylln goup

Looauanet al. (1998)100

randomzd tal o lo-do pntoxylln(0.83 [mg/kg]/h) u hgh-dopntoxylln (1.67 [mg/kg]/h) u placbo

45 Tha adult, 18 o hom hadcbal malaa

No dnc n DoC o motalty

Da et al.(2003)79

rDPCT o pntoxylln (10 mg/kgntanouly) o 3 day

52 indan adult thcbal malaa

shot DoC n pntoxylln goup (22 h) u placbogoup (64 h); dca n TNF ll by day 3 and tndtoad ducd motalty n pntoxylln goup

aAll patnt gn th antmalaal dug qunn, xcpt o om patnt n th an Hnbok tudy, ho gn a tmth. Abbaton; DoC, duaton o coma at tatmnt;FCT, claanc tm; HiG, hypmmun mmunoglobn; PCT, paat claanc tm; rDPCT, andomzd, doubl-blnd, placbo-contolld tal; TNF, tumo nco acto.





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dd b pd cc f h dyghyp. i d, fy qy f bd f dd 4 h pd bc f ccb fd d. th f xchg f c. th p bf f h cd pd f ccg p69 d h cpd h gh h d ffc (f xp, c), hcpby cc h dcg h k f ccy d. th wHo cd h

xchg f hd b cdd f h ph (dp c, hypgyc, cd ) h p f >20%. H, cc d b h d pdc h xchg f.

Adjctiv thap

i f h fc h dg f k 12–18 h k h p, djc hpdd h gh dc h k f y d cg q, pcy p h cb . a b f g hb bg d, b h h qc

dc f p cc (tb 1 d 2).Cqy, f h g c b cdd p f h dd g gy p.my f h py cdcd,70 d q d h dd dg f h. th c f djc hpy gh dff f dd cjc h .

Ccd -fy g hgh p h gy f h bd–b b,d dc bh c p d h f-y p. th cpd h fdjc g b d dzd, cd

. H, dzd f dff d f dxh sh e ad44,71 d id chd hcb 72 dd h y bf. i fc, f h , dxh cd hcd cpc (g bdg, pd pgd c cy ).44 th cpdh b d afc chd, h fxhb c hyp d h kd fy p h a d.

Dfx ch d c -xd. Py fdg Zb chd hcb dcd h h h dg cd h pd f f, dc- z d dcd d f c,73 b g, dzd hd ffc y.74 N -cy cy h xd, hch pyhcy dfby d hb tnF . thdg z c d h 75 d cy bg d d hcb .57

Pxfy dc c f cyk ch tnF, p g, c yhcy df-

by, d gh dc cydhc.76

a f h dg G h fc-p dd h y cc bf dc tnF ,77 b h dy dd ddCns cpc. i p-b, dzd, c-d, hpc 56 Bd chd h c-b , pxfy dcd bh h d f c d tnF .78 i 52 id d h cb, pxfy gfcy dcd h df c, h d d dc y. 79

i f h ppd c f tnF hphphygy f cb , f B-C7,

Table 2 | randomzd tal o omotc dutc, lud and phnobabtal n malaa th nuologcal complcaton

rfc Dsi ad ima Patits otcms

Osmotic diuretic therapy

Namutangulaet al. (2007)85

rCT o manntol (1 g/kg) a a ngl doon admon

156 Ugandan chldn th cbalmalaa

No bnft th pct to DoC, FCT o motalty

Fluids

Matland et al. (2005)86

randomzd tal o 4% albumn (20 ml/kg)u nomal aln (20 ml/kg) umantnanc (patnt th modatacdo only)

150 Knyan chldn th acdo,123 o hom had mpadconcoun

Lo motalty th albumn than th aln (4% 18%) n patnt th modat acdo; n patntth coma, 5% o tho gn albumn ddcompad th 46% o tho gn aln

Seizure prophylaxis

wht NJ et al. (1988)90

rDPCT o phnobabtal (3.5 mg/kg nglntamucula do) u placbo

48 Tha chldn (>6 ya old) andTha adult th cbal malaa

szu occud at admon n 54% o placbo 12.5% o phnobabtal goup

Kocha DL et al.

(1997)91 randomzd tal o phnobabtal (10 mg/kg ngl ntamucula do)

184 indan adult th cbalmalaa

szu occud at admon n 3% o phnobabtal goup 23% o placbo goup

Caly JC et al.

(2000)92

rDPCT o phnobabtal (20 mg/kg nglntamucula do) u placbo

340 Knyan chldn th cbalmalaa

szu occud at admon n 11% o phnobabtal goup 27% o placbo goup;motalty a 18% n phnobabtal goup u 8%o placbo goup

aAll patnt gn th antmalaal dug qunn. Abbaton: DoC, duaton o coma at tatmnt; FCT, claanc tm; rCT, andomzd, contolld tal; rDPCT, andomzd,

doubl-blnd, placbo-contolld tal.





reviews

c bdy g tnF, pfd Gb chd h cb . th g dd dc y, d , fh, cdh c gc q, pby bch bdy tnF h h cc, hchpg ffc h c dh.80

Hyp gb hb d h

cydhc f fcd yhcy in vitro. a f hyp gb, pfd f h p f c - bd d 31 m ch-d h cb , ppd bc hgb dd b p- pcb.81 oh cpd h f hcydhc, ch hp,72 cd f82 d,83 h b d p h ,cdg cb . cy bg d id d Bgdh d h .57

oc dc ch cp, d gh p cccy f d

dc xyg f-dc dg.84 m fd dc c p Ky ch-d h cb , b dd p pc.25 a g d f dd dcy f gc q ugdchd h cb ,85 d p d d p c d h cb (mh sK, pbhd d).

ab gh p cccy f d hyp, d hby dc cc cd.i chd h d cd, ph ii cc h ggd h 4% b p -y cpd h , pcy chd h

c.86

a g bg cdcd dd h f 4% b chd h p d .57 oh cd ch gf, dx 70 dhch bg xd.57 oh cpdh p cccy f, ch -dhp, dd p c id ch-d h cb . Dchc py dhydg, hch d dc c . i Gh chd h d hypc, dchc dd pc h h gc f.87

edc gg h yhp h -pc cb .88 a d h

h h c d-dpd, d dc bh h fy p h b d pp. rcy, chdh cb d hgh f yhp dd h gfcy b chcf g h gc q h chdh cb d yhp .89 a f h cpd chd h cb dy.57

Pphycc c gh p -c p h cb , pcy h gd cg q. a g

c jc f phbb dcd hfqcy f z th d,90 id d91 d Ky chd h cb .92 H,h cd h cd -y h chd, pbby bc dpd hhypp h y cp f cd h d p. a f fphy, hch h

f d pp h phbb, c-y bg cdcd.57

s h cpd ch pcy hb d djc hp p h c-b , b cc h b cdcd.a h p , ph ii cc f c- d chc dc dx, d l-g p dh fc, c cc d xyg dy,93 bg cdcd.57 ohcpd, ch g h p p ggg-,94 ,95 d,96 d ppcg,97 h b ggd djc hp, bh y b d h.

Future research

th phg f h gc cpc f fcp q fh cd. sdg mri, pcy h c d,98 gh b hpf h gd. eeG d h f z c f p c, d c bd h ffc f ppc dg. i hf, ff bh hghy pcfc df f cb b p, d g f c p d cb bdf gh b f h gd. th fhg f p djc hp, ch

ppc g, d, d cgp k f b dg hd b d c h d.

Conclusions

th gc cpc f fcp c d cp d pc f ccp. th cpc c f dgc , c p dg ccc.t f h gc cpc -d, b cdcd d, djc - h b h p h c f fcp .

Review criteria

PubMd a achd ung entz o atcl publhdbo 1 Nomb 2008, ncludng lctonc aly

la publcaton. sach tm ncludd “Plasmodium

falciparum” o “alcpaum malaa” o “cbal malaa”

and “ban” o “cntal nou ytm” o “nuologcal

complcaton” and “thapy” o “adju* thapy”. w choonly pap ttn n englh and Fnch, th languag

ad by th autho. in addton, achd th clncal

tal gt http://clncaltal.go/ and http://.

contolld-tal.com/mct/ th th tm “ malaa”.





reviews

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http://www.cdc.gov/malaria/diagnosis_treatment/clinicians3.htm


http://www.controlled-trials.com/










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Ackwdmts

s. K. Mha xp h nc thank toth Dcto o intn Ca (D O. P. Agaal),Dcto (D P. K. rath) and th ta o th MalaaUnt o ipat Gnal Hoptal, inda.C. r. J. C. Nton undd by Th wllcom Tut,UK, and h to thank h collagu n Knya andth UK ho ha contbutd to th da outlnd n

th r, and Kan v o hlp n thppaaton o th manucpt.

Documents

2009 Cerebral Malaria Nature Neurol Mishra & Newton