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SECTION 4 Malaria

P. falcioarum P. vivax P. malariae P. ovale P. knawlesi

Felative abundance

Natural host

Other hosts

lncubation period

Blood schizogonic

cycle

Latent hepatic stageGonnranh in

distribution

Parasitemia

RBC infected

0rgans infected

Salient syndromes in

severe drsease

Drug resistance

pr0Drems

Dormancy

Very common

HUMAN

r Some African apes

7-14 days

48 hours {tertian)

No

Subtropical and tropical

Americas, Africa, Asia

>1 00,000/pL dangerous

Any

Vascular sinuses

. Seizuresu

. Coma

. AKIb

. Jaundice/hepatic

dysfunctionb

. ARDSb

r Anemia"

r Shockr Metabolic acidosis

. Chloroquine

{ un iversal )

. Artemisinin

{Southeast Asia}

Rare

Very common

HUman

. Some African apes

. New World monkeys

1 0-20 days

48 hours (tertian)

Yes

Temperate, subtropical, and

tropical Americas, Af rica,

Asia

Does not correlate with

clinical threat

Youngest reticulocytes

Vascular sinuses, spleen,

and marn lv. Platelets <50,000/pL. Shock

. Jaundice/hepatic

dysfunction

. Severe anemia

. Metabolic acidosis

. AKI

. Coma

. Abnormal bleeding

. ARDS

. Splenic infarction/rupture

. Chloroquine (Southeast

Asia). Primaquine (Southeast

Asiai

Latent hypnozoites, about 1

month up to 4 years

Bare

Human

. Some New World

monkeys

1 !-30 days

36 hours (quartan)

No

Subtropical and tropical

Americas, Africa, Asia

Almost never high

0lder erythrocytes

Vascular sinuses and

unknown. Rare case reports of

AKI and AHDS

Bare

Human. Some African apes

1 1-1 6 days

48 hours {tertian)

Yes

Subtropical and tropical

Africa and Asia

Almost never high

Flotinr rlnnvfoc

Vascular sinuses and

unknown. ARDS

. Anemia

Rare

Macaques. Gibbons. Leaf monkeys

. Others

9-1 2 days

24 hours (quotidia-

No

Tropical Southeas:

Asia

>50,000/pL dan3e'r

Any

Vascular sinuses

. ARDS

. Jaundice/hepa:c

dysfunction. AKI

. Shock

o Metabolic acrr:s

None

None known

One report of

chloroquine resistance

in southern Sumatra,

Indones ia

As long as several

decades, mechanism

unknown

Unknown

Latent hypnozoites, but

durations unknown

"More common in children.bMore common in adults,AKl Acute kidney infection; ARDS, acute respiratory distress syndrome; RBC, red blood cell.

whereas that risk in nonimmune patients sharply increases with age.7

As another example, severe anemia appears commonly in endemic areas

with hospitalized malaria, but appears much less often in travelers withthe same diagnosis. This chapter sets aside these complexities by consider-

ing only the nonimmune traveler,

CLINICAL PRESENTATION OF

UNGOMPLICATED MALARIA

Onset of symptoms of uncomplicated malaria in the nonimmune patient

not taking chemoprophyiaxis is typically within 8-14 days after an

infectious anopheline mosquito bite. In most travelers diagnosed withfalciparum maiaria, clinical attack occurs within 1 month after travel

and cessation of suppressive chemoprophylaxis. Vivax malaria' on

the other hand, appears 2 months or more later because suppressive

chemoprophylaxis does not impact the latent liver stage hypnozoites

responsible for delayed attacks. Late falciparum attacks may alsc rbut are quite rare.

Fever occurs in almost all patients and is often preceded br- : i

prodrome of 1-2 days of vague abdominal discomfort, headache- =ache, and maiaise; cough is surprisingiy common (20o/o-50o/o). C:tmay be iethargic, anorexic, and irritable. On the other hand. u:third of patients with confirmed malaria may present afebrile .:the cyclic nature of paroxysms linked to the asexual reproductir:of parasites in the blood. Of those with fever, classic descriptior :of24,48,or 72 hours according to species (see Table 17.1) ratelr- ':in the nonimmune patient where daiiy paroxysm is the rule reg:::

of infecting species. The paroxysm may begin in the late afternoo:intractable vomiting followed by chills with profound shivering .a

a Jew hours. Those pass and then quickly progress to a spiking(39'-41.5'C) with drenching sweats ofseveral hours. I)eferves.er

eariy morning leaves the patient exhausted and finally able to ie

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'eruournaud'srlrraluaorlse8,ssaull aIrI-ezuengut u? se r{Jns sasou8erpraqlo roleJ 1eq1 su8rs pue suroldu.(s -(q paleunuop sl lpq] euo aq derucrnlcrd prrurl: Burluasa.rd aql pue suollelsaJrueur,(urru seq BrrEI"tr I,{rotrepueu sr uoqeurru€xe ierrs,Qd q8noroqt V .sesseulp ureuaf, trnoalnr o1 1ryd1aq sr sporrad uorleqn)ur eql Jo e8pal.rou) .petlnf,f,o el?r{,{eur srq} uouo Moq pue (ereiilvr ,uaq,{\ .suor}raJur raq}o pu€ err€luluo1 arnsodxa;o sanlf, ur?tqo o1 1ue1;odrur sr -{rolsrq poo8 y.peo.rq d.ra.L

sI srelelerl ur ralal palerlueragrpun etrn)e Jo srsou8erp prruarelJrp aql

N0rI3lJNH0 StS0NCVt0

u'sluarled palpeli-Sv AI 0lJo (o/oLZ) 6I ur perrn)f,o slql :uolsrTsu?:tr arrnbor -(eu qr1q.n ,(y11v)?Iruaue r1]dlouraq alnoe (o1ea.tr g,- o1 dn) pa.(e1ap sl (SV AI) ateunselresnoueleJlur qlmr sluarted ?rJ€leru eJalas (aunuturuou 3ur1ue.t1 ;oaluanbasuoc luepodrur au6 dlrprqroru pal?laJ-?rteleur 01 suorllaJurI?rra1f,?q (o/o9' 9l) parrnbre-plrdsoq pue (s1ua4ed yo g'1 ),Qrunuruo:

ac!punerpue ro^oj 19 pue ro^ol palelluerej

Jo uorlngrrluo: aq1 palq8rgSlq oq.tr ,.p F laaunrg Lq 1

'sluarled 00t Jo serras reruee u? urorJ esoql qlla luelsJsuolarp epp esaq; 'firptqrouror 8ur.(lrapun u? p?i{ sluarled;o o7o1

pue 'Z sp.r\ ?rJelrtr OH,,\4.Jo raqunu uerpaw aq1 u.(o7og) suoa1dr11nru (x) pue '(yog) eruraedlSod,(q (x1) .(o7og) srsopne (rrr.,

Surpealq snoaueluods (rr,r) .(oZoZt) SOUV/arnpe; Lrole:rdsar (r.r

>1ooqs (,r) '(o7o61) Anfut.bupr4 alnre (ti,@toSd ewof,/ssausrparednn (IU)' Q/oW) acrpune( (rr),(o7o I L-) o/og< erntelsered.radiQuaes sernl€eJ urprrr eql .(?ualuf,

OH,,1A 9002) ?rlEIDru arelas p,qlrm sluarled EgI Jo serres ueado;rng euo uI .(7.21 e1qe1) s:

f,ruapua-ertplpru ruorJ ?l?p uo.{llsour pasuq sr pue uarplr{l puqloq roJ €rralrrf, seq ?rftFtrr arelas Jo uorlrsgap (91q14) uorlerI{lletl{ ppo/A rq;'poqs rrld:s ptre srsd:s sp rlrns suouq)uof, raLelqeqsrnSurisrpn.(lexrqc s11eq1 ssauip rrtua1s,fu e;o su8rs pue su

flqlqxa ,bur pue 1a,rmn ,(1rea1c er? utreieru ere^as q]ftr Swlueserd

vtuvlvtu 0lIVctltoNV lUlAtS J0 N0|lVINlSlUd 1V3

'sarllleu:ouqe ,{'lraseql areqs suorlf,aJul prrdorl papodun raqlo Luery.quarledlopagodar sr (ur8rro 1ao par pue ra,trl:I{61) aseua8o-rp,{qap alepq .

'o/o8e vI urqnrrlrq plol sr s? ,s1uarled ;o o/og7 vl prsrpr ar€ ( [Jl

as€uftuesu?n ewrleie/eseunupsue4 alegedse) sarulzua tarnl .rue

rlnr 01 Pasn eq.ra^eu plnoqs pu€ (selbogdu,(1 1u:rd.{1e ,egrq<

'eruadoqdur.(1'eruedoursoe ,.8,a) alqerrea sr uoqeluasa;d 1e 1-JIp )f,nA ayl'O/o8Z'.IplE Zl> [3gg] urqolSouraq) enuaue'srsoldf,o{nel puu eruedo>1nalJo sa}er repurrs (,u) ,(.Iri/gOO,Oi-f

Iururou eqt ut (o/o0g ,f,)\A) lunor ile) atrqr\ p1o1 e (rrr) ,(o7oi

Tdl000'09> lunor p1a1e1d (II), @/o1g-o/r1V) eruadot-{roquorqr ;c,{ue (r) qlr.r,r. sluarled;o suorgodord aq} ro; ,tqpo,ru}ou aru s

rrSololeruag '(o7oy-) attpune( pue ,(oyo11-) ,(p8auroledeq ,r

.(pBauoualds'(as.rnoo ssaqp aqr 3ur:np s,tu.rp tsoury) ra aJ apnlognadsuou pue ,ral eJe erleleru palerrlduorun ur su8rs letrs

letr|rouqv sNc pue ro^aJpue ro^oJ

qseu pues!llr{uv -/+

JeASI

euelel^ LlllM ]uatled oql ol q3eot V TI U]IdVHC

SECTION 4 Malaria

lmpaired consciousness

Acidosis

Hypoglycem ia

Severe malarial anemia

Renal impairment/acute kidney injury

Jaundice

Pulmonary edema

Significant bleeding

Shock

Hyperparas item ia"

"There are no parasitemia limits for P

initiating effective antimalarial treatment would be consistent with the

clinical diagnosis of malaria, but confirmation nonetheless requires

laboratory evidence.

Microscopic Diagnosis. In most acutely ill patients' plasmodial

parasites may be observed in stained thick blood films examined by oil

immersion light microscopy ( 1000x) by technicians cerlified as comPetent

and having access to good-quality reagents and microscope' The thinfilm is most useful for quantifring hyperparasitemia and aiding inidentificdtion to species rather than the search for parasites. Guidance

for endemic laboratories typically demands examination of at least 200

ocular fields before declaring a slide negative for malaria. In nonendemic

clinics seeing nonimmune patients, that search should be much more

extensive (e.g., >500 fields and as many as 2000)' because nonimmune

patients have a far lower threshold of parasitemia for acute febrile illness.

It is often possible for the microscoPist to decide upon the species

observed employing a variety of visual clues. The banana-shaped

gametocltes of P. falciparum are pathognomonic, for example. Enlarge-

ment of infected red blood cells containing ameboid parasites points

to P. vivax or P. ovale, Mature schizonts may be seen and these offer

strong clues to species identity. However, the microscopist also faces

limitations in this regard. If only young ring forms are observed, a

specific diagnosis may not be possible' If the patient is infected by P

knowlesi, the microscopic diagnosis of it is virtually impossible-it ismost often mistaken for P, malariae but this species characteristically

presents with iow parasitemia rather than the frequently occurring

hyperparasitemia (>50,000/pL) of P. knowlesi malaria.

In most patients with malaria, clinical threat correlates with the

density of parasitemia, as is proven for P. falciparum and P, knowlesi

malarias with >100,000 and >50,000 parasitesipl blood' respectively,

each associated with an increased risk of severe disease. Howevet this

is much less clear in patients with P vivax malaria, where biomass may

sequester in the spleen and marrow.eJo Any level of parasitemia in vivax

malaria should be considered potentially threatening'

Rapid Diagnostic TestsA wide variety of commercially available immunochromatographiccassettes for the diagnosis of malaria may be applied where competent

microscopic diagnosis is not available. Though simple and often effective

in endemic settings, the diagnosis is less sensitive than expert

A Glasgow coma score <1 1 in adults or a Blantyre coma score <3 in children

A base deficit of >8 mEqlL or, if unavailable, a plasma bicarbonate of <15 mmol/L or venous plasma lactate >5 -rru[Severe acidosis manifests clinically as respiratory distress: rapid, deep, and labored breathing

Blood or plasma glucose <2.2nnoUL (<40 mg/dl)

A hemoglobin c0ncentration <5 g/dl or a hematocrit of <1 5% in children <1 2 years of age {<7 g/dL and <20%,

respectively, in adults) together with a parasite count >10,000/pL

Plasma or serum creatinine >265 pmol/L {3 mg/L) or blood urea >20 mmol/L

Plasma or serum bilirubin >50 pmol/L (3 mS/dL) together with a parasite count >100,000/pL

P. knowlesi jaundice as above and parasitemia >20,000/pL

Badiologically confirmed, 0r oxygen saturation <92% on room air with a respiratory rate >30/min, often with ches:

indrawing and crepitations on auscultation

Including recurrent or prolonged bleeding from nose, gums, or venipuncture sites; hematemesis or melena

Compensated shock is deflned as capillary refill >3 s 0rtemperature gradient on leg (mid to proximal limb), but nc

hypotension. Decompensated shock is defined as systolic blood pressure <70 mm Hg in children or <80 mm HE radults with evidence of impaired perfusion (cool peripheries or prolonged capillary refill)

P. falciparun parasitemia >10ok, P. knowlesi parasilefitd)2o/o

vivax

microscopy-few of the many available kits detect parasitemia <- -tirr.l

and iower sensitivity for P vivax malaria is qpical' No kit reveals pa-u

counts or stages present. Rapid tests designed to detect only P fal4'mhistidine-rich protein 2 (HRP-2) will be negative for all other srr:including P. knowlesi.Non-P. falciparum malarla can be detectec '*'rapid tests containing a pan antigen strip but tend to be less sexm

The problem of some strains of P /al ciparum in the wild having c3r:

their HRP genes renders them undetectable by HRP-basei :adiagnostic tests (RDTs).lr

Nucleic Acid Diagnostic TestsA wide variety of polymerase chain reaction (PCR) tests for the m:-ahave been described.l2 Most are sensitive to about one parasr:i :

microliter and may be species speci{ic, and quantitative tests :rrparasite load in examined tissues. PCR testing is far more sensi=':

mixed species infection than even expert microscopy. The pri:,:rdrawbacks are high levels of laboratory expertise, cost, and time rec-rn

A laboratory with all specialized reagents on hand typically requ-::least several hours and often an entire workday or more to report fi::;:lPCR diagnosis thus typically confirms an early diagnosis that S:rimmediate therapy.

TREATMENT OF UNCOMPLICATED MALARIA

Several options exist for treating malaria (Table 17.4). Choices de-':'r

on drug availability, parasite species, and local resistance parrThe most powerful antimalarial drugs are the artemisinin-de

combinations (ACTs), but some ACTs are unavailable in nonencg

countries. Chloroquine (CQ) is used commonly to treat P. lh;amalariae, P. ovale, and P. knowlesl. However, CQ-resistant P. rr::well documented in Southeast Asia' the Indonesian archipeiaga I

Papua New Guinea with reported foci in a range of countries. '

doubt, use an ACT. Although CQ is effective against uncompli;P. knowlesi, the ACTs are more rapidly acting and are preferred tirinfection with a tendenc.v to produce rapidly severe disease' Atoraq.-:,

proguanil is available widely and retains efficacy against P. falcip;'(faiiures reported from rvestern Cambodia), P , vivax, and P. knowles:.

individuals who have been taking chemoprophylaxis, typically dor-cline, atovaquone proguaril, or mefloquine, treatment should ex;these druss.

ppoqs slualt?d'a8eleal,heipdur l..reuorulnd P3s€arrul ol anp Pas?elf, ur

sr ?uepe ,Lreuoulnd Suqeltdnard p€olla o pln6 Jo {sll aq} Jsnelaq

]ueuodun fl a)uelEq plnu ol aoua8qt6 'l?Irnlf, st luarled {lls aI{J Jo

J.rec Sursrnu poog 'spadse .(a1 rq8rq8rq a1{ (rolaMoll fr*allal slql

;o adors oi{} puoiaq st sluarled qtrns Jo }uaura8eueru pap?laP er{J

'r'tsulTlg sI

]unor altsered oi{l pue .{11errut1r Bunordrut aq o1 readde sluarled 3r

ua,re (s,{ep € aiur} u€rparu) ;a1e1 srn,o scuv :zpa}uaunJop II3M

arr (1yy) ,fun(ur Lauprl alnr? pue (Le.n.rre aq] ]oalord o1 prpaeu

uor]€Ilual lecrueqcaur) elruleru Iurqeraf, o1 (s.rnoq p7 eu\l uetparu)

uor1erolratap prde: asneraq ,(1rea sueal leuer puu n)I aql ilaN'(nCI) lF n Jr?f, ellsualur u? ro ]Iun Lruapuadap q8rq e ur peB?ueul

Jq plnoqs EIJe]etu aJalas qlr.^\ stuarled llY'JatlletuEue Jeln,snureJlul

VlUVtVl/ll lUlAlS l0 tNllilllfliil

€ r'lU : : ;:-'llllllll!!l

luarledlno :o; areld ut slorolord seq lPql ltun lstletrads ; .- ilrrol

paref, are .{aql ssapn s}uar}ed pa}feJul-unltdnp; }sou: : ' rilLilil'

-snup? puouruo:ar sauqeptnB tuarul?erl erlel€W )n ai{I --T:l lnmr

as?asrp arales Surdola,tap Jo {sIJ Pes?aJf,ul u? le are (1ri - '

o/oz< slsnor altse:ed qlli{ asoqi puu.{prder a}sJolla}aP uE: :-.-r:lmlri

pepaJur-?IrPlsru aunulunuou :uoqe^lasqo aso]l JoJ 1e$dsoq o:: - -Tlrajeql llurpe ol Jar{}aq-4{ sI Dleru o} a €q suzlllurll uolsl))p .ier- : - .

ro suorsryui aurutnbasn-,ra>1 sr lueluleerl

esn 'alq?lr€^?un II '(E'lI alqP: :' i,

prde; Lq pe/t{olloJ }uJrussrss? fei:.- rlmilnt

a^oqe sva^oqe sv

a^oqe sv

0^0qe sv

a^oqe sv

'asesslp leual ole^as ul ploAV

'urui/lur 09> ocuelealc aululleals qIlM 0s0p acnpou

{sate}S pailun} sleoA B>'(LuoP0ut;poltun) slea^ zt> palecrputerluoc x00 0)ll lou

Aeu uarpltqc ieql alse] lelll6 uouutoc ulslu0q3ulS :N0

ol,\sv aos'uue!eM

+0 i3a]la

1ueln0eocr1ue €ql scuequa Aeu 94 sloltqtqut eseelold

pue'zuar^era'surlolserlal'aptueid0leolau'ullnqelll'u13!duiejlj Aq pocnpal slo^al Alv aseeslp la^ll

ala^as ur elep 0N ultlnul 0t> asuelealc aulullealS']uaui.lledtxl

leual ara^aS (3 to g a0e1s q0nd-pllq3 'slsoqlllc

pelesuaduocap ' a r) oseoslp ia^ll a.lo^os '(stuo]du^s

pue ocrpune[) aseaslp lo^ll olnse pa]e3lpurei]u03

'stlluotL.l z> asop

]eador 0N /isdalrda '{stsolnau Alatxue 'uorssaldap)

eseasrp culerqc^sd luec[tu0ts ul paleslpulPlluo3

srlruruJgsuer] pue elusdollnsu lualsuell sasnes /ilaleu

c16 Duol

LllrM aseosrp e o^eq lo snnjp u0 '/{1rue; lo lualled ul

uollebuolold ciO leUuaouoo uMoul :suolleolpulelluoC'le^rolur 310 aq] +o uolleou0lold luapuedap asop dd

's0nlP

uorleouol0id c10 uo/qllM sluolled s0nlp telr^o4allluepue srornpul tVtdIS Aq palca+,e sl0^01 lV :suollneJ

'sralo^ertr ul a^ll3a]la 0n'9d-Alv'03'a^rlco]]a ddvHo pue'lv'OIASV

'aratlMasla l30l elsv ls 'eaulne

MaN ended 'ersouopul ut uouruoc U03'su0rlepu0ujru0c0l

lecol M0lloj 9-9-9-0[ r0

9-01-01 :srnoq gy ut 017011 gZ osop lelol

's^ep g lo] uo^|0

oq lieu aururnp sAep 1 to; q]oq a^tg's^ep

Z ja^o

0176r! gg uaq] 9L :6)/0u 9Z asop lelol

'%z< erualrsejed

! papuourtuocol 10N spueq 0ulsop

rnoj uOrldlosqe Alv aseal3ul ol luupi!1ru ro pool qllM alet 0utsop Altep acug

'sol n u eJ0

to1 6ursop aoiql pue (0I 0Z< ]q0ra^ )

slalqel ro] spueq 0utsop JnoJ slqelle^e

salnuel0 cr4elpad 0ulsop Altep acug

s13V raqlo ueql ssal i{1t;tqele;01

llero^0 spuPq outsop tnol etsy

3g ur acueuadxa 1soy1 butsop Altep acug"spueq 0ursop rnol

'eculv ur pasn Ilapl6 Outsop Altep acug'spueq 0ursop 1q0r3 uoridrosqe

dd sacuequa poo; Apel asneceq

qceuols Aldua ue u0 alel spuottltxo3al

raln]seJnuen 0utsop /tllep acug'sPueq 0utsoP

rnol uotldrosqe auuluelaunl asealcul

0t luup/)cPus AllP, q]lM Allep 03lMi elel

a3ue::;a

0t (03) aulnboi. -: rttu

xeLlA unlpoutga3

(xoc + N0)

aurlc^cMop + eululn0

(Oy\) aurnboBof!

'UOlleUlquloc pgseq-ululsl!:--, F

sltelop aloLu lol sllosut e6e>1ced ,sletnlce+nueuJ ]solel oql ]lnsuo3 'pauolluguJ ele suolleclpulelluoc/suollne3 - : * -.,*

0L\ '9d-Atv '03 luauleall a' ::--E-reAOqe se s13V ]uaullPe]].- ::.,lL'*

lsaynou\ IunlpoLu*

gd-A1v r0 0^0qe slcv luauleoil e^:3-,8-$ti

eur nborol q3 lUAUleArl a- j,r:a e lre pw .un lp o u$ e Id :ale^ o .u n lp o {uf'l'k

gd-Al_v l0 0^0qe sl3v (u03) acuels !:. :x

(9d-Arv)

lruen0ord auonbenoly

oleunsalie

autPUeuolri4

(0WSV)

eurnbopeu aleunsouv

eu rnbetpotle

aleunsauv

(46y116)autnbetadtd

-uru rsruap eolp,{qt6

nv) auulueiaunl

Jaqloulsuv

]u0ulear] aAlleL.:--r

luauleoJl aurl ]s-:wntedplel unlpouseH

llnec saloN

euelel^ qllM luolled oLll ol qceol V lt UAIdVHC

Malaria-

Artesunate

Artesunate children

Artemether

0uinine salt

2.4 mg/kg ar0h,12h,24h2.4 mg/kg dailt/

3 mg/kg at 0h,12h,24n3 mg/kg dailY

3.2 mg/kg lM on 0 h

1.6 mg/kg 24 h

1.6 mg/kg dail}'

20 mg/kg infused over 4 h

4 h off infusion

10 mg/kg infused over 4 h

4 h off infusion

10 mg/kg infused over 4 h

4 h off infusion, etc.

Give for a minimum of 24 h

C0ntrnue treatment unlil the patiBnt can eat and drink

Treat with an ACT at standard dose

0uinine can be infused in crystalloid (e g , dextrose 5%, dextrose sa -:

Give for a minimum of 24 h

Monitor glucose every 2 hours during infusion

Continue treatment until the patient can eat and drink

Treat with an ACT at standard dose

Give IM into anterior thigh if venous access is challenging

be kept "dry" while maintaining adequate perfusion and renal function'

An input-output chart is essential, but a central venous-pressure line

is ,roi,rsefril ln guiding fluid management' Reserve aggressive fluid

resuscitation for patients who are shocked but stiil exercise caution and

observe carefully for a response. Limit the number of fluid challenges

and seek early ICU advice regarding the use ofvasopressors' Shock in

se,rere -alu.iu may be due to a concurrent bacterial infection' which

also contributes to metabolic acidosis and the development of ARDS.

Tinke blood and other cultures and treat promptly with a broad-spectrum

antibiotic. AKI in severe malaria is hypercatabolic and eariy renal

replacement treatment may be needed' Con'ulsions should be managed

in the standard way; look for and correct hypoglycemia' hypocalcemia'

hyponatremia, andhypoxia' Hypoglycemia may occ:rr in severe malaria'

particularly in quinine-treated patients even in-the recovery phase'

Regular blood glucose concentrations by fingerstick are necessary: every

4 hours routinely, every 2 hours during quinine infusions' and at any

time a patient has a convulsion and/or reduced level of consciousness'

Treat hypoglycemia acutely with 10olo dextrose and prevent further

epi.od", with S o/o ot l0o/o derlrose infusions as part of fluid maintenance'

futt Ulooa counts, clotting, and biochemistry (including calcium'

magnesium, and phosphatej should be monitored closely' especially ifAKi develops. Daily malaria parasite counts are needed to monitor

parasite clearur-tc.. Biood transfusion should follow local ICU guidelines'

Piatelet transfusions are not inclicated even with low counts unless there

is active bleeding.

IFSIUEH9f*S-IY-FIEUS!=$I!A$l*ct!!!'p-LE"]I--Most of the experience of pediatric severe malaria cornes from sub-

SaharanAfricawherethecofilmonmanifestationsarecerebralmalaria'severe anemia, and acidotic- and dehydration-driven respiratory distress'

Convulsions, hyperpyrexia' and hypoglycemia frequently complicate

the ciinical couise. Maitiand et a1'15 have published guidelines for

managing nonimmune children.

hypoglycemia (which may be recurrent with quinine treatmen: :

oit..l*lt. uncomplicated disease, malaria in the second anC : - '

trimesters should be treated with an ACT; they are effective 31; "'rIn the first trimester, 7 days of quinine combined with clindamvc-: '

'

recommended. Recent data, however, show similar miscarrias' --

stillbirth rates for quinine and ACT treatments in the first trir:-"-:'

For severe maiaria, IV AS is the drug of first choice in all trin":'"using the same dose as in nonpregnant adults' Primaquine shou': -

be given to a Pregnant woman.

ANTIRELAPSE THERAPY WITH PRIMAOUINE

TREATMENT OF MALARIA IN PREGNANCY

Presumptive antirelapse therapy (PART) with primaquine pt "'.o-ple* challenge to the effective treatment of P' vivax and P ' ' '

A11 patients diagnosed with these infections should be conside:':

riskof multiple recurrent attacks up to about 2 years follortir': -i

primary attack. The frequency, timing, and number of secondaq' a:: ' -' '

varies with geographic origin ofthe infection, but in general th:s -

occur in at least 30% and often over 80o/o of patients' Each re:. ' :

attack is as debilitating and potentially dangerous as the primarr ":- -

Prescribing PART to Prevent relapses is strongly recommended br''"' :based on very good evidence.

Primaquine was registered for PART in combination with chlor":' - "' 'for the raiical cure of vivax malaria ln 1952 at a dose of 15 m5 : "daiiy in adults for 14 <lays commencing concurrent with chloroc'- '

therapy or within 1-2 weeks of completing it' Most authorities ::': '

,eco-mend 30 mg daily in an adult for i4 days because of its : -'effrcacy and the poor efficacy of the 15 mg dose in tropical stra.:.'

P. vittax.t6 Taken with a snack or meal, the former is remarkab't "and well tolerated in nonpregnant patients aged >6 months i:' '-

normal glucose-6-phosphate dehydrogenase (G6PD) activin' \a

upcoming discussion).' Some patients prescribed PART and who strictiy adhere to r: :- '

nonetheiess suffer relapses of vivax or ovale malarias as a conseq -: - -':

of relatively poor metabolism of primaquine to its active meta: ;

by cytochrome P-450 isozyme 2D6 (CYP2D6)' That isozyme is h:--

polymorphic and the efient of primaquine metabolism may be imi' -'''

or nuil according to the CYP2D6 alleles present' Repeated ot incr" " 'dosing may achieve cure in the former, but not in the latter' Th' ' -

metabolizer cannot be cured of the latent stages of these mai': -

Ascertaining CYP2D6 genotyPe in patients who fail PART shou': :"

undertaken.

Pregnant women with malaria are Prone to severe disease and suffer

mislcarriages and stilibirths' Involve the obstetric and pediatric teams

early. In ih" ,..ond half of pregnancy, malaria can be a fulminant

disease associated with a higher mortality than in nonpregnant women'

Two features of severe mllaria stand out in pregnancy: ARDS and

ACI. Artemisinin-based combination; h, hour(s); /M intramuscular

'ev-Lettr€,et9002

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sf,#T?#g"d d Malaria

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