pocket guidelines for the care of malaria patients · pathogenesis, and guidelines for patient...

Pocket Guidelinesfor the Care

ofMalaria Patients

Suparp Vannaphan

WHO Collaborating Center for Clinical Managementof Malaria

Faculty of Tropical Medicine, Mahidol UniversityBangkok, Thailand

First Edition 2009; 3000 copies,Printed and Published byWHO Collaborating Center for Clinical Management of MalariaBangkok, Thailand

All rights reserved. No part of this may be reproduced, stored in a retrieval system or transmitted in any form or by any means without the prior written permission of the copyright owner.Printed in Thailand.

Publication Data

Pocket Guidelines for the Care of Malaria PatientsP. cm.Include bibliographies and index.Vannaphan, Suparp

ISBN 978-974-11-1075-9

Contents

Preface 4Acknowledgements 5Introduction 6Map 7Part 1: The science of malaria in humans 8 Life cycle 9 Pathology 11 Pathogenesis 16Part 2: Nursing care of malaria infected patients 17 Early detection 17 Early treatment 22 Referral 27Part 3: Algorithm 31 Fever with negative blood film 31 Fever with positive blood film 32 Severe malaria 33 Cerebral malaria 34 Respiratory failure 35 Acute renal failure 36 Jaundice 37 Disseminated intravascular coagulation 38 Fever 39 Hypoglycemia 40 Prevention of secondary bacterial infection 41 Severe anemia 42 Hemoglobinuria 43 Health education 44 Algorithm Index 45Bibliography 46Index 47

Preface

This is the first set of pocket guidelines produced by theWHOCollaboratingCenter forClinicalManagementofMalaria fornursing care in the treatment of malaria. The contents compriseepidemiologicaldataregardingmalaria,basicmalariapathologyandpathogenesis,andguidelinesforpatientcare,includingclinicalcare,diagnosis and referral. It covers emergency treatment and effectivenursingcareduringthepre-referral,transfer,andpost-referralperiods.Inaddition,theseguidelinescontainalgorithmsforthemanagementofmalaria. Thisbooklet canbeused tohelpnurses care forpatientswithmalaria,enablingthemtorecovermorerapidly,andreducemorbidityand mortality rates from malaria. The nurse must have a soundknowledgeofthepathophysiologyofmalariaandshouldbesensitivetotheneedsofthepatient.Expertcarebythephysician,combinedwithgoodnursingcare, isneededtohelpthepatient recover fully.Research regarding new medication and medical care techniqueswill provide better management of malaria, resulting in a betterprognosis. Ihopethisbookletwillbeofbenefittobothnursesandpatients.

SuparpVannaphan,BScNursingTheHospitalforTropicalDiseases,FacultyofTropicalMedicineMahidolUniversity,Bangkok,ThailandFebruary2009

� Pocket Guidelines for the Care of Malaria Patients

Acknowledgements

I would like to express my thanks to Assoc. Prof. PratapSinghasivanon, Dean of the Faculty of Tropical Medicine, MahidolUniversity,forhiscontinuoussupportduringthepreparationofthisbook.ThanksalsotothelateProf.SornchaiLooareesuwan,Prof.PolratWilairatana,Prof.SrivichaKrudsood,Prof.NicholasJ.White,Assoc.Prof. Parnpen Viriyavejakul, Assoc. Prof. Pornthep Chanthavanich,Asst. Prof. Watcharee Chokejindachai, and Dr. Nick Walters, forreviewing this booklet. I would like to thank Assoc. Prof. SuvaneeSupavejforhermanyhelpfulsuggestionsforimprovingthisbooklet.Iwouldalsoliketothankmyparents,teachersandthepatientswhohavehelpedmetogaintheknowledgetowritethisbooklet.IwouldliketoacknowledgetheWHOSEAROfortheirgeneroussupportinthe printing of this booklet, without whose financial support, thisbookletwouldnothavebeenpublished.

Pocket Guidelines for the Care of Malaria Patients �

Introduction

MalariaiscausedbyprotozoanparasitesofthegenusPlasmodium,themostserious formbeing thespeciesP. falciparum.Patientswithseveremalariahave15to20%mortality. Itisestimatedthat300-660millionclinicalepisodesofP. falciparummalariaoccurred in2002(Snowet al.,2005).Previouslyextremelywidespread, malaria is now mainly confined to tropical regions ofAfrica,AsiaandLatinAmerica.Theproblemofcontrollingmalariainthesecountriesisaggravatedbyinadequatehealthinfrastructuresandpoorsocioeconomicconditions. The treatment of this condition requires hospitalization andsometimesintensivecare.Thesignsandsymptomsofseveremalariaarenon-specificandcanoccurwithotherseverefebrilediseasessuchasmeningitis,encephalitis,septicemia,typhoidfever,leptospirosisandviralinfectionswhicharecommonlyseeninmalariousareas.Inviewofthenon-specificpresentation,itisdifficulttorecommendastandardclinicalcasedefinitionforthedisease.Furthermore,thetreatmentofseveremalaria involvestheuseofmedicineswhichmaybetoxic.P. falciparum is becoming increasingly resistant tomany antimalarials.Thediagnosisofmalariabymicroscopyor rapiddiagnostic tests isveryimportant. Severe malaria should be treated in an intensive care unit, ifpossible.Inahospitalwherenecessaryequipmentforthemanagementofseveremalaria,suchasventilatorsforthemanagementofrespiratoryfailure,isnotavailable,thepatientshouldbereferredtoahigherlevelhospital.


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Part 1: The science of malaria in humans

Fig. 2 Lifecycleofmalaria(AdaptedwithpermissionfromAssist.Prof.Chotechuang

Panasoponkul,DepartmentofMedicalEntomology,FacultyofTropicalMedicine,

MahidolUniversityThailand).

Liver cells

Hyp

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Mature pre-erythrocytic SchizontIiberating merozoites

Merozoite Trophozoite

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erythrocytic stage Schizont

Merozoite

GametocytesInfective stage(Sporozoite)

MosquitoSalivary gland

Mosquito midgutOokinete 17

Fertillzation

Macrogamete Microgamete Exflagellation

Developing oocystsMature oocystswith sporozoites


Life cycle

Theinfectiveagentisthesporozoite,whichisinjectedintohumansbythebiteofan infectedfemaleanophelinemosquito.Sporozoitesdisappear fromthebloodwithin1hourandenter livercellswheretheyproliferateintomerozoitesandtheexoerythrocyticcyclestarts.Development in liver cells requires1-2weeksdependingupon thespeciesofPlasmodium (P. falciparum andP. vivax1week,P. malariae andP. ovale2weeks,nodataatpresentforP. knowlesiinhumans).InP. vivaxandP. ovale,somesporozoitesremaindormant(hypnozoites)formonthsoroccasionallyayearormorebeforeproliferation(relapse).Afterreplicationintheliver,parasitesundergoasexualmultiplicationintheerythrocytes.Themerozoitesinfecterythrocytesandconstitutetheerythrocyticformsoftheparasite.

Erythrocyticparasitedevelopment can follow twopathways. Inthe first pathway, asexual parasites develop from young ring formsthrough trophozoites and schizonts, which subsequently rupture,then reinvade erythrocytes. The erythrocytic cycle of schizogony isrepeatedover andover again, thus continuing the cycle ofmalariainfection. In the second pathway in P. falciparum infection afterapproximately1week,someerythrocyticparasitesdifferentiateintomaleandfemalegametocytes,thusenteringthesexualpathway.Whenmale and female gametocytes are ingested by female mosquitoesduringabloodmeal,fertilizationoccurs,resultinginazygote,whichpenetrates themosquitomidgutwall to formanoocyst containingsporozoites. When oocysts mature (10-14 days), they rupturereleasingsporozoites,whichinvadethesalivaryglandandarereadytobe injectedback intohumans, completing themalaria life cycle(White,2000).Table1 shows the characteristicsofP. falciparum, P. vivax, P. ovaleandP. malariae.ThedetailedcharacteristicsofP. knowlesiinhumansarenotavailableintheliteratureatpresent.


Table 1.Characteristicsof4speciesofhumanmalaria(Looareesuwan et al.,1990)

P. falciparum P. vivax P. ovale P. malariae

Pre-erythrocyticstage(days) 5.5 8 9 14-15 Presenceofhypnozoites - + + - Pre-patentperiod(days) 8-25 8-27 9-27 15-30 Incubationperiod(days) 12(9-14) 15(12-17) 17(16-18) 28(18-40) orupto6-12 orlonger orlonger months Erythrocyticcycle(hours) 48 48 48 72 Natureofhosterythrocyte All Reticulocytes Reticulocytes Normocytes andyoung andyoung normocytes, normocytes Duffygroup positive Enlargementofhosterythrocyte - ++ + - Parasitemia/mm3

Average 40,000 2,000,000 20,000 50,000 Maximum 9,000 30,000 6,000 20,000 Primaryattack Severein Mildto Mild Mild non-immune severe Febrileparoxysm(hours) 16-36 8-12 8-12 8-10 orlonger Relapse - ++ ++ - Periodofrecurrence Short Variable Variable Verylong Durationofuntreated infection(years) 1-2 2-5 2-5 3-50 Stripplingofhosterythrocyte Maurer’s Schüffner’s Schüffner’s Ziemann’s clefts dots dots strippling

10 Pocket Guidelines for the Care of Malaria Patients

Pathology

In fatal falciparum malaria, autopsy specimens usually showcerebral edema. Brain herniation and brainstem compression canhappen,butthisoccursinlessthan5%ofcases(Fig2a)(Looareesuwanet al.,1990).Cutsurfacesofthebrainrevealpetechialhemorrhages(Fig2b).Microscopically,minutepetechialhemorrhagesarefrequent,particularlyinthewhitematter(Fig3a).Themicrovasculatureofthevitalorgansispackedwitherythrocytescontainingmatureformsoftheparasite.Bloodvesselsbecomeoccludedduetosequestrationofparasitizedredbloodcells(PRBCs).TheprocessofsequestrationispossibleduetotheattachmentofPRBCstothevascularendothelium(Fig 3b). Sequestration is not uniformlydistributed; it tends to begreatestinthebrainfollowedbytheheart,lungs,andsmallintestine(Pongponratnet al.,1991).

There isabundant intra-andextra-erythrocyticpigmentdepositinvitalorgans,suchastheliver(Fig4a),spleen,andplacenta.Intheliver, thesehemosiderinpigmentsareseentobepackedwithinthesinusoidalareas(Fig4b).Thekidneysoffatalmalariacasesoftenshowcongestionandareasofpetechialhemorrhage(Fig5a).PRBCs,aswellas hemosiderin pigment, are densely found within the glomerulartufts(Fig5b).

Pocket Guidelines for the Care of Malaria Patients 11

Fig. 2 Brainofcerebralmalaria.a)Brainedemawithherniationcanbeseen.b)Cut

surface of the cerebrum shows dispersed petechial hemorrhages, particularly

in the white matter (Courtesy, Department of Tropical Pathology, Faculty of

TropicalMedicine,MahidolUniversity,Thailand).


Fig. 3 Microscopicfindingsofcerebralmalaria.a)Petechialhemorrhagesarefrequently

foundinthewhitematter(arrow)(H&EstainX100).b)Parasitizedredblood

cellsseenwithinthevascularlumenmostlycytoadheretoendothelialcellslining

thevascularwall(arrow)(H&EstainX400)(Courtesy,DepartmentofTropical

Pathology,FacultyofTropicalMedicine,MahidolUniversity,Thailand).


Fig. 4 Liverof severemalaria case. a)Liver is grossly enlargedandappears asdeep

browntored.Capsularhemorrhagesareseen.b)Microscopicfindingofliver

showingparasitizedredbloodcellsandhemosiderinpigmentspackedwithin

the sinusoids (arrow) (H&E stain X400) (Courtesy, Department of Tropical

Pathology,FacultyofTropicalMedicine,MahidolUniversity,Thailand).

1� Pocket Guidelines for the Care of Malaria Patients

Fig. 5 Kidneyofseveremalariacase.a)Cutsurfacesshowhemorrhagicappearance.

Petechialhemorrhagesarefrequentlyfound.b)Microscopicfindingofkidney

showingcongestedglomeruliandpresenceofpackedparasitizedredbloodcells

(arrow)(H&EstainX400)(Courtesy,DepartmentofTropicalPathology,Faculty

ofTropicalMedicine,MahidolUniversity,Thailand).

Pocket Guidelines for the Care of Malaria Patients 1�

Pathogenesis

Feverinmalariaresultsfromthereleaseoftumornecrosisfactor(TNF) and other endogenous cytokines in response to parasiteantigens. Signs and symptoms of malaria are associated with theruptureofparasitizederythrocytes.Inseveremalaria,tissuehypoxiais believed toplay an important role leading toorgandysfunction.However, the pathophysiological mechanisms are still not clearlyunderstood,especiallyincerebralmalaria.Duringthepast30years,manyhypotheseshavebeenput forward toexplain this condition.It is thought that sequestration of parasitized erythrocytes, thephenomenon of cytoadherence, rosette formation, and reducederythrocyte deformability, lead to microvascular obstruction, andalongwith the effectof cytokines contribute to tissuehypoxia andorgandysfunction(Looareesuwanet al.,1997).


Part 2: Nursing Care of Malaria Patients

A. Early detection Earlydetectionandcorrecttreatmentandnursingcareofmalariapatientswillresultinlowermortalityandmorbidityrates.Themortalityrateforcerebralmalariavariesfrom5-20%dependingonconcomitantmajororgancomplications.Earlydetectionshouldbeaccomplishedby careful evaluationof thehistory and correct examinationof thepatient. Thick and thin blood films should be examined. Antigendetection/striptests[bloodforP. falciparumHistidine-RichProtein-2 (Pf HRP2) or P. falciparum Lactate Dehydrogenase (Pf LDH)] arevaluablefortherapiddiagnosisoffalciparummalaria(WHO,2006).

1. History Asktherelativesorresponsiblepersonswhetherthepatienthastraveledtoamalariousarea,hasahistoryofmalariainfection,chronicmalaria, or has taken any anti-malarial drugs prior to admission/consultation.Ifso,checkthebloodfilmmorefrequently(ifthepatienthasrecentlytakenmedication,thebloodfilmmaybefalse-negative).Atleastthreenegativebloodfilmsareneededtoruleoutadiagnosisofmalaria.Askifthepatienthasreceivedabloodtransfusion.Evenifthepatienthasnevertraveledtoamalaria-endemicarea,buthasreceivedabloodtransfusionorhasworkedinalaboratorywithmalariainfectedblood,theyareatrisk.Ithasbeenreportedthatthosewholivenearanairport,eventhoughthereisnomalariaintheircommunity,cangetmalariafrommosquitoescarriedbyairplanes.Thosewhoworkinaninsectiarywithmosquitoesmayalsobeatriskofmalariaifinfectedmosquitoesbitethem.


2. Physical examination The level of consciousness should be graded using either theModifiedGlasgowComaScaleforadultsorBlantyreComaScaleforchildren.Monitorvitalsignsandurineoutput,andlookforevidenceofshock.Lookforevidenceofanenlargedspleen,whichcouldindicateapreviousmalariainfection.Lookforsignsofanemiaandbleeding,and prepare for blood transfusion, if necessary. Patients who havereceivedquinineorarejaundiced,andwomeninlatepregnancy,areatriskofhypoglycemia.Monitoringbloodglucoseinthesepatientsisessential.Inpatientswhoremainseverelyill,thedoseofquinineshouldbe reducedonday3byone third.Frequently evaluate thenervous system for level of consciousness (hourly) (Training Unit-WHO,1995;HarinasutaandBunnag,1988).


Evaluation of level of consciousness with cerebral malaria based on the Modified Glasgow Coma Scale

(Adaptedfrom:RegionalGuidelinesfortheManagementofSevereFalciparumMalariainSmallHospitals,WHO,NewDelhi,2006)

Modified Glasgow Coma Scale for adults

Eyes open Spontaneously 4 Tospeech 3 Topain 2 Noresponse 1 Best verbal response (Nonintubated) Orientedandtalks 5 Disorientedandtalks 4 Inappropriatewords 3 Incomprehensiblesounds 2 Noresponse 1

(Intubated) Seemsabletotalk 5 Questionableabilitytotalk 3 Generallyunresponsive 1 Best motor response Verbalcommands 6 Localizestopain 5 Withdrawstopain 4 Decorticate 3 Decerebrate 2 None 1 Total score 3–15

Totalscore=eyeopeningscore+verbal(intubatedornonintubated)score+motorscore

Totalscorerangesfrom3to15;unrousablecomareflectedinascoreof<9.

Thisscalecanbeusedrepeatedlytoassessimprovementordeterioration.


Blantyre Coma Scale for children(“Blantyre Coma Scale”)

Eye movements Directed(e.g.towardsmother’sface) 1 Notdirected 0Verbal response Appropriatecry 2 Inappropriatecryormoan 1 None 0Best motor response Localisestopainfulstimuli 2 Withdrawslimbfrompain 1 Non-specificorabsentresponse 0Total score 0–5

Totalscorecanrangefrom0-5;2orlessindicatesunrousablecoma.Thisscalecanbeusedrepeatedlytoassessimprovementordeterioration.


3. Differential diagnosis Those who have altered consciousness must be evaluated forhypoglycemia,renalfailure,electrolyteimbalance,andpost-ictalstate.Examinethebloodsugar,BUN,creatinine,electrolytes,liverfunctiontestsandurineanalysis.Abloodcultureshouldbetaken.

Those with cerebral malaria will have a reduced level ofconsciousness.Priortoalteredconsciousness,thepatientsmayhavebeenhighfever,bodyaches,headache,nausea,vomitingorabdominalpain. After that, the consciousness level can deteriorate, resultingin confusion, decreased responsiveness, no communication orincontinence.Theremaybegeneralizedorfocalseizures,disconjugategaze or muscle twitches. The clinical signs and symptoms may besimilar toencephalitisormeningitis.A lumbarpunctureshouldbeperformedtodifferentiatebetweencerebralmalariaandothercentralnervoussystem(CNS)diseasesafteranormaleyegroundexamination(Warrell,1997).

�. The diagnosis of malaria Perform thick and thin blood films for malaria. The thick filmismorelikelytodetectasmallernumbersofparasitesthanthethinfilm,becausethethickfilmusesmoreblood.Thethinfilmisusefulindetectingthespeciesofmalaria,%infectedredbloodcells,stageofparasitedevelopment,andpresenceofneutrophilpigment(>5%ofneutrophilscontainingpigmentindicatesapoorprognosis)

Usually, the higher the percentage of infected red blood cells,themoreseriousthecaseis.However,someseverepatientsmaynothavehyperparasitemia, probablydue toperipheral sequestrationofthe parasite in the brain or other vital organs. Ideally, the numberofparasitizedredcellsper1,000RBCs(thinfilm)orthenumberofparasitesper200whitecells(thickfilm)shouldbereported.


Malaria Rapid Diagnostic Test (RDT)

TheRDTisarapidtesttoevaluatethepresenceofmalariaantigensin the blood of a patient suspected of having malaria. Some RDTcheck for P. falciparum only, while others check for other malarias.Thetestmaybeastrip,card,orcassette.Thetestsaresensitiveandas accurate as microscopy. They are good for people who do nothaveamicroscopeavailable,havenoelectricity,orwherenooneistrainedtouseamicroscope.However,theWorldHealthOrganization(WHO,2004)recommendsthatafterstartingtreatment,managementdecisionsshouldnotbebasedontheRDTalone.Aconfirmatorytestshouldbeperformedwithmicroscopy.

B. Early treatment

Thetreatmentofmalariaisseparatedinto2groups:uncomplicatedandcomplicatedmalaria.

1. Uncomplicated malaria. The patient has no signs ofcomplications.Thetreatmentconsistsof: A.Earlyandappropriateantimalarialmedication.Thechoiceofmedicineshouldbebasedonthedrugsensitivitiesofthemalariaparasites in that area. Artemisinin-based combination treatmentsarenowrecommendedasfirst-linetreatmentforfalciparummalariaby theWorldHealthOrganization(2006).Quininecombinedwithdoxycycline,fornon-pregnantadultsandchildren>8yearsold,orclindamycinforpregnantwomenandchildren<8yearsoldgivenfor7daysaresecond-linetreatments.Thefirsttreatmentdoseshouldbeobserved.Ifthedoseisvomitedwithinonehour,itshouldbegivenagain.


B. Symptomatic treatment. Treat symptoms, such asfever,bodyaches,nausea,vomitingorheadaches,withappropriatemedicine.Paracetamol(acetaminophen)(15mg/kg4–6hourly)maybeusedtoreducefever.

C. Nursing care. Give supportive care and symptomatictreatment, such as tepid sponging for fever. Give health educationregardingpersonalprotection,preventionofmalariaandcompliancewithtreatment.Thepatientshouldbetoldtoreturnifthereisfever,especiallyinthe2monthsaftertreatmentorwithP. vivaxorP. ovale infection. The patient should be advised to take the full course ofmedicationtopreventareturnofmalaria.Ifthereisvomitingoftheantimalarialdrug, take an antiemeticmedicine½ to1hourbeforetaking the antimalarial drug. If there is fever, take an antipyretic 1hourbeforetakingtheantimalarialmedicine.Thepatientshouldrestfor1–2hoursaftertakingthemedicine,duetotheriskofdizziness,vomiting,andhypotension.Thepatientshouldbegivenpsychosocialsupportbyencouragingthepatientandgivingcomfort.Allcasesofmalaria shouldbe recordedand reported to the appropriatehealthauthorities to help in the control of malaria. The patient shouldfollowupwiththedoctortoevaluateforcompliance,thetherapeuticresponsetothedrugandtoevaluateforevidenceofdrugresistance.


2. Complicated (severe) malaria: TheWHO(2006)criteriaforseveremalariaareasfollows:

Clinical manifestations: -Prostration -Impairedconsciousness -Respiratorydistress(acidoticbreathing) -Multipleconvulsions -Circulatorycollapse -Pulmonaryedema(radiological) -Abnormalbleeding -Jaundice -Hemoglobinuria

Laboratory tests: -Severeanemia -Hypoglycemia -Acidosis -Renalimpairment -Hyperlactatemia -Hyperparasitemia

Someexpertsdefinethelaboratorytestsasfollows:severeanemiaisaHb<5g/dl,especiallywith>100,000parasites/µl;hypoglycemiaisaserumglucose<2.2mmol/lor<40mg/dl;acidosisisaHCO3< 15 mmol/l; renal impairment is a serum creatinine > 3 mg/dlor250µmol/l;hyperlactatemiaisaserumlactate>5mmol/l;andhyperparasitemiais≥ 5%.


Antimalarial drugs in severe malaria (WHO, 2006)

Antimalarial Dosage and drug administration

Artemisinin derivatives

Artesunate: 2.4 mg/kg body weight (bw)intravenous(IV)orintramuscular(IM)onadmission(time=0), followed by 2.4 mg/kg at 12 and 24hours,followedbyoncedailyfor7days.Oncethepatientcantolerateoraltherapy,treatmentshouldbe switched to a completedosageof artemisinin-based combination therapy (ACT) for 3 days, asrecommendedinthenationaltreatmentguidelinesforuncomplicatedmalaria.Artemether: 3.2 mg/kg bw IM on the first dayfollowedby1.6mg/kgbwdailyfor7days.Oncethepatientcantolerateoraltherapy,treatmentshouldbeswitchedtoacompletedosageofanACT.Arteether: 3.2 mg/kg bw IM on the first day,followed by 1.6 mg/kg bw for the next 4 days.Once thepatientcan tolerateoral therapy, switchtoacompletedosageofanACT.

Quinine Loading dose: Quinine dihydrochloride 20 mgsalt/kgbwdilutedin10ml/kgbwof5%dextroseordextrosesalineadministeredbyIVinfusionovera period of 4 hours. Maintenance dose: Quininedihydrochloride10mgsalt/kgbwdilutedin10ml/kgbwof5%dextroseordextrosesalineadministeredbyIVinfusion.Inadults,themaintenancedoseisinfusedoveraperiodof4hoursandrepeatedevery8hours.Inchildren,itisinfusedoveraperiodof


2 hours and repeated every 8 hours (calculatedfromthebeginningofthepreviousinfusion)untilthe patient is in a position to swallow. An oralmedicationcanbegivenfollowingthis,tocompletethe 7-day treatment. The amount of fluid forinfusionofquinineshouldbeconsideredkeepingin mind the hydration status of the patient. Forinstance, if the patient has volume overload orpulmonary edema, quinine in 10 ml/kg IV fluidmaybeharmful.Therefore,thecalculationoffluidforquinineinfusionshouldbemadeaccordingly. Forchoiceoforaldrugsforfollow-ontreatment,it is recommended to prescribe a combinationtherapy:3daysofACTaccording to thenationaltreatment guidelines. If ACT is not in use in thecountry, quinine should be administered incombination with tetracycline or doxycycline orclindamycin, to complete the 7-day treatment,except for pregnant women and children <8yearsof age, forwhom tetracycline/doxycycline iscontraindicated.


Refer patient to a hospital with better facilities to care for severe malaria Indicationtoreferseveremalariapatients.Thedecisiontorefera patient with severe malaria is based on the ability of the facilityto give appropriate management for severe malaria. This includesmedications, hemofiltration or hemodialysis, artificial ventilation,multiple transfusions, treating pregnant women, postpartumpatients,multi-organfailure,activebleeding,andcerebralmalarianotrespondingtoappropriatetreatmentwithin48hours.

•Pre-referral. Provide information to the family, guardian andpatient about the diagnosis and treatment plan. Explain that thediseasecanbelethalifnottreatedearlyandproperlyinthehospital.Knowwheretoreferthepatientandhowtotransferthepatientsafely.Makesurethereferralfacilityhastheabilitytoperformdialysisandhas a ventilator for the management of respiratory failure. Checkbloodglucosebeforetransfer. When referring to another hospital, if possible, communicatedirectly with the hospital personnel about the patient’s diagnosisand condition. Send all information, laboratory results, malariasmearslidesandotherstudiesofthepatientwiththemtothereferralhospital. If possible, send the patient by ambulance with oxygen,medicinetocontrolbloodpressure,convulsions,andhypoglycemia.Adoctorornurseshouldaccompanythepatienttomanageproblemsduringtransport. Giveantimalarialdrugsbeforetransport.TheyshouldbegivenbyIV injection (artesunate), or rectal artesunate if possible. If quinineisgiven,itmustbegivenbyrate-controlledinfusionorIMinjection,since gastrointestinal absorption in severe malaria is poor and thepatientmayaspirate(Winstanley,2001).If thepatienthasreducedconsciousnessor respiratoryproblems, intubatebefore transport. Ifthepatienthasanuricrenalfailure,thenhemofiltrationordialysismayberequired.


•During transfer.Maintaincontinuouscloseobservation.Givelifesupportbasedontheconditionofthepatient.Forexample,iftheoxygenlevelisloworthereisdyspnea,giveoxygen.Monitorintakeandoutputpreciselyinmillilitersperhour,byplacingaFoleycathetertomonitorurineoutput.Providepsychosocialsupportforthefamilyandpatientbyexplainingwhatishappeningandthatifthepatientreceivescorrectandearlytreatmenttheywillrecover. Makesuretheairwayissecure.Ifnoventilatorisavailable,giveoxygenbymask.Positionthepatientsotheairwayisclear.Suctionto clear the airway, as necessary. Use an oral airway as necessary,especiallywithbagandmask. Monitorthebloodpressure,pulse,intakeandoutputfrequently.IftoomuchIVfluidisgiven,fluidoverload(positivefluidbalance),and eventually pulmonary edema, may result. If too little IV fluidis given (negative fluid balance), renal insufficiency or failure (pre-renalazotemia)mayoccur.MaintainaFoleycathetertomonitorurineoutput. Monitorforhypoglycemia,particularlyinseveremalariapatients,whenusingquinineorintreatingpregnantwomenandchildrenbyfollowingbloodsugarlevelsregularly.Insertanasogastrictube(NG)andgiveglucoseviaNG tube.Stopping IVdextrose suddenlymayresult inhypoglycemia, especially inmalnourishedpatients.GivingglucosebymouthorbyNG tube is less likely to result in suddenhypoglycemia. If referral isnotpossible,maintain theaboveadvice.Treatmentwithearlyandcorrectantimalarialdrugsisthemostimportantfactortoimprovesurvival. Treatfeverwithtepidspongingandantipyreticdrugs.Inchildren<5yearsold, thismayprevent febrileseizures.Prevent falls from,andinjuriesin,bed. Thehematocritlevelshouldbefollowed.Thereisariskofsevereanemia with complicated malaria and hyperparasitemia. When


hyperparasitemia and a low hematocrit are present, if possible,crossmatchandprepareforabloodtransfusion.Bloodisusuallygivenifhematocrit<20%.If there isaconcomitant lowserumalbuminlevel,givepackedredcellswithserumalbuminorwholeblood. If there is severeanemiaand thepatient is volumeoverloaded,givepackedredcellsandadiuretic. Givedextrose10%byIVifbloodsugarislow. If there are seizures, givediazepamasneeded tocontrol them.Considerphenobarbitalorphenytoinonlyif facilitiesforventilationare available. Hypoglycemia can cause seizures. Check the glucoselevel to rule this out if there are seizures, and if present, treat asmentionedabove. If the patient is short of breath, look for other evidence ofpulmonaryedema,suchascrackles in the lungs.Check the intakeandoutputrecordforapositivefluidbalance.Ifpulmonaryedemaispresent,giveadiureticandconsiderusingacolloid,especiallyforthosewithlowserumalbumin.

• Post-referral care. After the patient returns from treatment,theyneedtofollowupforperiodicbloodmalariachecks.Iftheyhavefeverafterleavinghospital,checkandevaluateabloodfilmformalariaforrelapseorrecrudescence.Encouragethepatienttocompletethecourseofdrugs.

•Prevention.Educate thepatientand familyaboutpreventivemeasures.Use amosquitonet, repellent,mosquito coil, orfire, todecrease bites. Stay indoors at night during the malaria season. Ifgoingout,coverthearmsandlegs.Residualmosquitosprayingtheinsidewallsofthehousecanhelptoreducebites.

• Advice for travelers. Besides the prevention advice alreadymentioned, travelersmaychoose tousemalaria-chemoprophylactic


drugs. Commonly used drugs for prophylaxis include: mefloquine(Lariam®),doxycycline,atovaquone-proquanil(Malarone®).Chloroquine,inmostpartsoftheworld,doesnotprotectagainstfalciparummalaria.PrimaquineisusedafteraninfectionwithP. vivaxorP. ovale,topreventrelapse(Wilairatanaet al.,1997). Malarial chemoprophylactic drugs are not 100% effective, andtheymayalter thehistoryandmasksymptomsofmalariapatients.Incubation periods may be prolonged and the drugs may induceresistance (Wilairatana et al., 2002). They may also cause a falsenegativebloodsmearformalaria. If there is ahistory of travel to amalaria-endemic area, even ifmalariachemoprophylaxiswastaken,thereshouldbeahighindexofsuspicionformalaria,evenwithanegativebloodfilm.

• No malaria. If no malaria is found, other causes of illnessshouldbeinvestigatedandtreatedaccordingtotheetiology.Ifthereisnoclinicalconfirmationofanotherdiseaseandthereisahighriskofmalaria,thepatientmaybetreatedashavingmalaria.Iftheystillhavefever andhavebeen suspectedofmalaria, a bloodfilm formalariashouldberepeatedfrequently.


Part 3: Algorithms

Fever with negative blood film

Fever

Peripheralbloodsmear

Negative

Lookforother causesoffever

Noothercausefound Othercauses

Ifriskofmalaria Givespecific repeatbloodfilms6-hourly treatment

Health education Refer to Table 2

Algorithm 1 Sequential guideline for patients suspected of havingmalaria,presentingwithfeverandnegativebloodfilm.


Fever with positive blood film

Fever

Bloodfilm

Positive Positive Positive Positive Positive P. falciparum P. vivax P. malariae P. ovale P. knowlesi

Uncomplicated

Ifthepatientcantakeoraldrug Ifthepatientcannottakeoraldrug

Giveantimalarial Admit drugorally Giveantiemeticand Advisetotakeall antipyreticIM/IV themedicineand followupin2days Giveantimalarial Giveantimalarialdrug orearlierifthe drugorally parenterallyifunable patientdeteriorates totakeorally Checkbloodfilm Repeatbloodfilm dailyuntilnegative Recordintakeand formalariauntil outputtoprevent negativebloodfilm fluidimbalance thenfollowup Takecomplete bloodfilmondays antimalarialdrugand 7,14,21,and28 followupbloodfilm ondays7,14,21 and28


Algorithm 2 Sequential guideline formalariapatientpresentingwithfeverandpositivebloodfilm.


Severe malaria (WHO criteria)Severemalaria

Ifunabletomanagecomplicationsofseveremalaria,e.g.respiratoryandrenalfailure,thenrefertohigherfacilityhospital

Beforereferral

GiveantimalarialdrugIV/IMorsuppository,giveantipyreticandantiemetic,asneeded

Ifreducedconsciousness,intubatebeforetransfer

Duringtransfer: •Giveoxygen •Maintainairway •Havesuctionavailable •Havedextroseavailableforhypoglycemia •Haveanticonvulsantmedicineavailableforseizures •HaveIVlineinplace •HavereplacementIVcatheteravailable •PlaceFoleycatheterbeforetransport

Athospital

Admitdirectlyintensivecareunit(ICU)withoutdelay

Placeonrespirator •Repeatbloodfilm •Doarterialbloodgas •Dolabs* •Monitorvitalsigns,neurologicalsignsandfluid intakeandoutput •Continueantimalarialdrugs

Cerebralmalaria Acuterenalfailure DIC** Hypoglycemia Severeanemia

Respiratoryfailure Jaundice Fever Preventsecondary Hemoglobinuria bacterialinfection

**DIC=Disseminatedintravascularcoagulation Algorithm 3 Sequentialguidelineformanagementofseveremalaria.

Labs* - Electrolytes,including Plasmabicarbonate - Completebloodcount(CBC) - Serumbloodsugar - Liverfunctiontest - Bloodureanitrogen(BUN), creatinine - CXR(chestx-ray) - U/A(urineexam) - HIVtestforacute renalfailurepatients


Cerebral malaria

Cerebralmalaria

Ruleoutothercausesofaltered consciousness 1. Hypoglycemia:checkbloodsugar 2. Meningitis/encephalitis:dolumbar punctureifnocontraindication forlumbarpuncture. 3. Post-ictalstate 4. Metabolicacidosis

Intubate

•Followbloodsugar •Keepairwayclear •Monitorvitalsignsfrequently •Monitorneurologicalsigns •Treatconvulsions •InsertNGtubeforfeeds •InsertFoleycatheter •Monitorintake/output •Preventaccidents–siderails •Changepositionofpatientevery2hours


Algorithm 4 Sequentialguidelineformanagementofcerebralmalaria.


Respiratory failure

Respiratoryfailure

ARDS* Pulmonaryedema

- Arterialbloodgas - Recordintake/output - CXR - Diuretic - UsePEEPventilator - Arterialbloodgases - Propuptheheadofthe - Ifgivingblood, patient45o givediuretic - Followintakeand - Keepheadofbedup output - Balancefluids - Ifbloodtransfusionneeded totreatanemia,use packedredcells(PRC) insteadofwholeblood

Health educationRefer to Table 2

*ARDS=AdultrespiratorydistresssyndromeAlgorithm 5 Sequentialguidelineformanagementofrespiratoryfailure

inseveremalaria.


Acute renal failure

Acuterenalfailure

Excludedehydrationstatusandrehydratethepatient

Recordintake/outputCheckbloodforBUN/creatinine

Renalfailureconfirmed

Dialysisindications?

Yes No

Hemofiltration/ Conservativetreatment dialysis ofrenalfailure

HealtheducationRefertoTable2

Algorithm 6 Sequentialguidelineformanagementofacuterenalfailureinseveremalaria.


Jaundice

Jaundice

CheckliverfunctiontestLookforassociatedviralhepatitisinfections

Lookforothercomplicationsofseveremalaria,suchashypoglycemia,hemolysisandrapidfallofhemoglobinneededforbloodtransfusion.


Algorithm 7 Sequentialguidelineformanagementofjaundiceinseveremalaria.


Disseminated intravascular coagulation (DIC )

DIC

CheckforRBCmorphology,hematocrit, hemoglobinuria,etc. Observeforevidenceofabnormalbleeding,e.g. subconjunctivalhemorrhage,epistaxis,bleeding pergums,petechiae,bleedingfrominjectionsites, hematemesisormelena.

Givereplacementtherapywithblood orbloodcomponents,e.g.freshwholeblood, packedredcells,freshfrozenplasmaorplatelet concentrate. Monitorintakeandoutputforrenalfailure.


Algorithm 8 Sequential guideline for management of disseminatedintravascularcoagulationinseveremalaria.


Fever

Fever

Monitortemperaturefrequently. Monitorforseizures,especiallyinchildren <6yearsold.Giveparacetamol (acetaminophen).Usetepidsponging, coolingblanket.Removeblanketsandsheets. Ifseizures,preventaspirationandinjury byplacingonthesideandgivediazepamor phenobarbital.


Algorithm 9 Sequential guideline for management of fever in severemalaria.


Hypoglycemia

HypoglycemiaBloodglucose<40mg%

Lookforconsciousnesslevel

Altered Asymptomatic consciousness hypoglycemia

50%glucose 50ccIVpush

Preventfurtherhypoglycemia byintravenousinfusion of5-10%dextrose

Frequentmonitoring ofbloodglucose


Algorithm 10 Sequentialguidelineformanagementofhypoglycemiainseveremalaria.

�0 Pocket Guidelines for the Care of Malaria Patients

Prevention of secondary bacterial infection

Preventionofsecondarybacterialinfection

Inseveremalariawithshock orunexplaineddeterioration,takeblood culturesandgiveappropriateantibiotics e.g.third-generationcephalosporin.


Algorithm 11 Sequentialguidelineforpreventionofsecondarybacterialinfectioninseveremalaria.

Pocket Guidelines for the Care of Malaria Patients �1

Severe anemia

Severeanemia

Typeandcross-matchbloodonadmission. Followhematocritlevel.ReplacewithPRC orwholeblood.Diuretic(furosemide) maybegiventopreventvolumeoverload. Transfusebloodslowlytoavoidvolumeoverload andpulmonaryedema.Balancefluidintake andoutput.


Algorithm 12 Sequentialguidelineformanagementofsevereanemiainseveremalaria.

�2 Pocket Guidelines for the Care of Malaria Patients

Hemoglobinuria

Hemoglobinuria

Followintakeandoutputandbalancefluids. Followhematocritlevel.Prepareblood transfusionifthereisanemia.CheckBUN, creatinineandelectrolytes.

CheckGlucose-6-phosphatedehydrogenase (G6PD).PatientswithG6PDdeficiency arevulnerabletothiscomplication.


Algorithm 13 Sequentialguidelineformanagementofhemoglobinuriainseveremalaria.

Pocket Guidelines for the Care of Malaria Patients �3

Health education

Table 2 Healtheducationfortreatedmalariapatients.

Health education ❐Takemedicineuntilcompleted. ❐ Iffeveroccurswithin2monthsaftertreatment, followuprightawaytoruleoutmixedinfection, resistanceorrecrudescence. ❐ Ifthepatienttraveledtoamalariaendemicarea andhasafeverwithin2weeksto2months aftertravel,beawareofriskofmalaria. ❐ IfthepatienthasG6PD,educatepatienttoinform thedoctorbeforetakinganymedicine. ❐ Preventionofmalaria. •Useinsecticide-treatedbednets. •Useresidualinsecticide. •Avoidgoingoutatnight;uselongsleeves andlongpants. •Userepellenttopreventmosquitobites.

�� Pocket Guidelines for the Care of Malaria Patients

Algorithm Index

Feverp.31

Postivep.32 Bloodfilmformlaria Negativep.31

WHOcriteria Lookforother Forseveremalariap.33 causesp.31

No Yes

Cantakeoraldrugs Refertohospitaliffacilities areinadequatep.33 Yesp.32 Nop.32 InICU,p.33

Giveantimalarial Giveantimalarial Stillunableto orally parenterally takedrugorally

Followupand Giveantimalarial Giveantimalarial repeatbloodfilm antimalarial antimalarial untilitisnegative, drugorally drugparenterally ifpossible

Healtheducationp.44

Cerebral Respiratory Acuterenal Jaundice DIC Malariap.34 Failurep.35 failurep.36 p.37 p.38

Fever Hypoglycemia Preventionof Severe Hemo- p.39 p.40 secondarybacteria anemia globinuria infectionp.41 p.42 p.43

Health education p.44

Algorithm 14 Summaryofsequentialguidelinesinthemanagementofseveremalaria.

Pocket Guidelines for the Care of Malaria Patients ��

Bibliography

HarinasutaT,BunnagD.Theclinicalfeaturesofmalaria.In:WernsdorferWH,McGregorI,eds.

Malaria: Principle and practice of malariology. Vol 1. Great Britain: Churchill Livingstone,

1988:709-32.

LooareesuwanS,WilairatanaP.Malaria.In: RakelRE,eds.Conn’sCurrentTherapy.Philadelphia:

WBSaunders,1997:104-15.

LooareesuwanS.Malaria. In:LooareesuwanS,BunnagD,HarinasutaT,eds.TheTextbookof

TropicalMedicine.Bangkok:RuamthasaPublishers,1990:39-44.

PongponratnE,RigantiM,PunpoowongB,AikawaM.Microvascularsequestrationofparasitized

erythrocytes inhuman falciparummalaria: apathological study.Am J Trop Med Hyg 1991;

44(2):168-75.

SnowRW,GuerraCA,NoorAM,MyintHY,HayS,I.Theglobaldistributionofclinicalepisodes

ofPlasmodium falciparum malaria. Nature2005;434:214-217.

TrainingUnit,DivisionofControlofTropicalDiseases.Thediagnosisandmanagementofsevere

andcomplicatedfalciparummalaria,part1:Learner’sguide.Geneva:WHO,1995:1-93.

WarrellDA.Cerebralmalaria: clinical features,pathophysiology and treatment.Ann Trop Med

Parasitol 1997;91:875-84.

WhiteNJ.Malaria. In:CookGC,ZumlaAI,eds.Manson’sTropicalDiseases.21sted.Geneva;

WHO,2000;1-69.

Wilairatana P, Looareesuwan S, Walsh DS. Chemotherapy of cerebral malaria: current

recommendationsfortreatmentandprophylaxis.CNS Drugs1997;7:366-80.

WilairatanaP,KrudsoodS,TreeprasertsukS,ChalermrutK,LooareesuwanS.Thefutureoutlook

ofantimalarialdrugsandrecentworkonthetreatmentofmalaria.Arch Med Res2002;33:

416-21.

WinstanleyP.Chemotherapeuticoptionsformalaria.Lancet Infect Dis2001;1:242-50.

WHO.GuidelinesfortheTreatmentofMalaria.Geneva:WHO,2006.

WHO.Managementofsevereandcomplicatedmalaria:apracticalhandbook(2nded.).London:

WBSaunders,2003:1-69.

WHO.Theuseofantimalarialdrugs.Geneva;WHO2000:5-141.

WHO.TheUseofMalariaRapidDiagnostictests.2004,(Cited2008Jan31).Availablefrom:

URL:http://www.searo.who.int/LinkFliles/Malaria_in_the_SEAR_RDTGuidelines_final1.pdf

WHO,TheWorldMapofMalariaandDrugResistance.2006,(Cited2008Feb25).Available

from:URL:http://www.who.int/malariaendemiccountries.html


Index

Acidosis24

Antimalarial22,25,27,28,32,33,45

Antipyretic23,28,32,33

Anemia18,24,28,35,42,43,45

Anticonvulsant33

Antiemetic32,33

Artemisinin22,25

Artesunate22,25,27

Artemether25

Arteether25

Arterialbloodgas33,35

Asexual9

Bednets44

Brainedema12

Cerebralmalaria12,17,21,33,34,45

Chloroquine29

Colloid29

Convulsion27,34

Coma 18,19,20

Cytokines16

Dialysis27,36

Diazepam29,39

Diuretic 29,35,42

Dizziness23

Drugresistance23

Disseminatedintravascularcoagulation

(DIC)33,38,45

Epistaxis38

Erythrocytes9,10,11,16

Encephalitis21,34

Electrolytes21,43

Fever 16,21,23,28,32,33,39,45

Gametocytes9

Hypnozoites 9,10

Hypoxia16

Hypoglycemia18,21,24,27,28,33,37,40,45

Hypotension23

Hyperparasitemia21,24,28,29

Hyperlactatemia24

Headache21,23

Hemodialysis 27

Hemofiltration 27,36

Hematocrit28,29,42,43

Hemoglobinuria24,33,38,43,45

Intubate27,33,34

Jaundice 24,33,37,45

Kidney11,15

Larium®29

Lumbarpuncture21,34

Merozoites9

Meningitis21,34

Melena38

Malarone®29

Mosquitocoils29

NGtube=nasogastrictube28,34

Nausea21,23

P. falciparum 9,10,11,22

P. knowlesi 9

P. malariae 9,10,32

P. ovale 9,10,29,32

P. vivax 9,10,23,29,32

Prophylaxis29

Parasites9,21

Paracetamol23,39

Pocket Guidelines for the Care of Malaria Patients ��

Phenobarbital29,39

Pregnancy18

Petechial11,12,13

Quinine18,22,25,27,28

Relapse30

Renalfailure21,27,33,36,38,45

Referral27,33

Respiratoryfailure27,33,45

Resistance23,30,44

Recrudescence29,44

Sporozoites 9

Schizont9

Sequestration11,21

Seizures21,29,33

Shock41

Trophozoites9

Treatment22,23,25,28,44

Unrousable19,20

Vomiting21,22

Volumeoverload29,42

Ventilator27

Zygote9

Index


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