WHO/CDD/94.

49
Original:English
Distr.:General

THEMANAGEMENTOFBLOODYDIARRHOEAINYOUNGCHILDREN

WorldHealthOrganization
ProgrammefortheControlofDiarrhoealDiseases
Geneva,Switzerland

WorldHealthOrganization1994
ThisdocumentisnotaformalpublicationoftheWorldHealthOrganization(WHO),andall
rightsarereservedbytheOrganization. Thedocumentmay,however,befreelyreviewed,
abstracted,reproducedandtranslated,inpartorinwhole,butnotforsaleoruseinconjunction
withcommercialpurposes.Theviewsexpressedindocumentsbynamedauthorsaresolelythe
responsibilityofthoseauthors.

TABLEOFCONTENTS

1.INTRODUCTION...............................................................................................................4
2.DEFINITIONS....................................................................................................................3
2.1Bloodydiarrhoea..................................................................................................3
2.2Dysentery.............................................................................................................3
2.3Invasivediarrhoea................................................................................................3
3.CAUSESOFBLOODYDIARRHOEA...............................................................................4
3.1Invasivebacteria...................................................................................................4
3.1.1Shigella................................................................................................4
3.1.2Otherinvasivebacteria.........................................................................7
3.2Entamoebahistolytica..........................................................................................7
3.2.1Invasiveamoebiasis..............................................................................7
3.2.2Luminalamoebiasis..............................................................................8
3.3Noninfectiouscausesofbloodydiarrhoea............................................................8
4. NATURAL HISTORY OF BLOODY DIARRHOEA AND ITS RESPONSE TO
TREATMENT...........................................................................................................9
4.1Shigellosis............................................................................................................9
4.2Bloodydiarrhoeacausedbyotherinvasivebacteria............................................10
4.3Intestinalamoebiasis..........................................................................................10
5.5.DETERMININGTHEETIOLOGYOFBLOODYDIARRHOEA.............................................11
5.1Basedonclinicalfeatures..................................................................................11
5.2Basedonmicroscopicexaminationofstool........................................................11
5.3Basedonstoolculture........................................................................................12
6.PRINCIPALSTEPSINTHEMANAGEMENTOFCHILDRENWITHBLOODY
DIARRHOEA.................................................................................................................................13
7.DETAILEDASPECTSOFCASEMANAGEMENT........................................................14
7.1Detectionofbloodydiarrhoea.............................................................................14
7.2Antimicrobialtherapy........................................................................................14
7.2.1Rationale............................................................................................14
7.2.2AntibioticsforShigella.......................................................................16
7.2.3Antimicrobialsforbloodydiarrhoeacausedbyotherinvasive
bacteria.......................................................................................................18
7.2.4Antimicrobialsforinvasiveamoebiasis..............................................18
7.2.5Misuseofmetronidazole....................................................................20
7.3Fluids.................................................................................................................20
7.4Feeding..............................................................................................................20
7.5Followupandreferraltohospital.....................................................................21
8.OTHERMEASURES........................................................................................................22
9.ACKNOWLEDGEMENTS...............................................................................................23
10.REFERENCES.................................................................................................................24

1.INTRODUCTION
Bloody diarrhoea in young children is usually a sign of invasive enteric infection that carries a
substantialriskofseriousmorbidityanddeath. Thisisespeciallytrueinthedevelopingcountries,
wheretheproblemoccursmostfrequently.Noninfectiouscausesaccountforaverysmallproportion
ofepisodesofbloodydiarrhoea.

About10%ofdiarrhoealepisodesinchildrenunder5yearsofagehavevisiblebloodinthestool,and
theseaccountforabout15%ofdiarrhoeaassociateddeathsinthisagegroupworldwide(1).Compared
withwaterydiarrhoea,bloodydiarrhoeagenerallylastslonger,isassociatedwithmorecomplications,is
morelikelytoadverselyaffectachild'sgrowth,andhasahighercasefatalityrate(24).

Studiesincommunitiesandhealthfacilitieshaveshownthatthemanagementofpatientswithbloody
diarrhoeaisfrequentlyirrational.Manymedicationsprescribedareineffectiveordangerous,andwhen
aneffectivemedicationisadvisedtheamountgivenisoftentoolittle,thedurationoftreatmenttoo
short,orboth(57).Oralrehydrationsalts(ORS)solutionisrecommendedinonlyasmallproportionof
casesandtheamounttakenisofteninsufficienttopreventdehydration(5).Foodalsomaybewithheld
orgiveninreducedamounts.

Thecorrecttreatmentofbloodydiarrhoearequiresthatmothersrecognizetheproblemandseekmedical
carepromptly,andthathealthworkersdispenseanappropriateantibiotic,giveORSsolutionorother
fluidstopreventortreatdehydration,adviseonappropriatefeeding,andprovidefollowup,especially
forchildrenatincreasedriskofseriousmorbidityordeath.Whencorrecttreatmentisgivenpromptly,
mostepisodesofbloodydiarrhoearesolverapidlyandseriousconsequencesareusuallyavoided.

Thisdocumentdescribessimpleandeffectiveguidelines,andtheirrationale,forthemanagementof
bloodydiarrhoeainchildrenbelowage5years,especiallyamongoutpatients.Thesearebasedoncase
managementguidelinesoutlinedintheWHOchart, Managementofthepatientwithdiarrhoea (1992
version),andinotherWHOdocumentsandpublications.

2.DEFINITIONS

Thefollowingdefinitionsapplytotermsusedinthisdocument.

2.1Bloodydiarrhoea

Thisisaclinicaldiagnosisthatreferstoanydiarrhoealepisodeinwhichthelooseorwaterystools
containvisibleredblood.Thisdoesnotincludeepisodesinwhichbloodispresentinstreaksonthe
surfaceofformedstool,isdetectedonlybymicroscopicexaminationorbiochemicaltests,orinwhich
stoolsareblackowingtothepresenceofdigestedblood(melena).
2.2Dysentery

Thishasthesamemeaningasbloodydiarrhoea,i.e.diarrhoeawithvisibleredbloodinthestool.This
simpledefinitionhasbeenusedinmostcommunitybasedstudies.Althoughclinicaltextsoftenusethis
term to describe thesyndrome of bloodydiarrhoea withfever, abdominal cramps, rectal painand
mucoidstools,thesefeaturesdonotalwaysaccompanybloodydiarrhoea,nordotheynecessarilydefine
itsetiologyordetermineappropriatetreatment.

2.3Invasivediarrhoea

This refers to diarrhoea caused by bacterial pathogens that invade the bowel mucosa, causing
inflammationandtissuedamage. Thiscausesnumerouspolymorphonuclearleucocytes(PMNs),and
sometimesredbloodcells,toappearinthestool.Thesecanbedetectedbymicroscopicexamination.
Thestoolmayalsocontainvisibleblood,butthisisnotnecessarytodiagnoseinvasivediarrhoea.When
visiblebloodispresent,theepisodecouldalsobetermedbloodydiarrhoeaordysentery.

3.CAUSESOFBLOODYDIARRHOEA

Amongyoungchildrenindevelopingcountries,mostepisodesofbloodydiarrhoearesultfromintestinal
infection,andnearlyallofthesearecausedbyinvasiveentericbacteria. Entamoebahistolytica,the
onlyimportantnonbacterialpathogen,usuallyaccountforlessthan3%ofepisodes(3,8).

3.1Invasivebacteria

3.1.1Shigella

Shigella is the pathogen most frequently isolated from the stools of young children with bloody
diarrhoeaindevelopingcountries(3,8),andtheterms"shigellosis"and"bacillarydysentery"areused
interchangeably.Shigellacause50%ormoreofallepisodesofbloodydiarrhoeainyoungchildren,and
amuchhigherproportionofepisodesthatareclinicallysevere(8,9).Inareviewofcasestreatedover
14yearsattheInternationalCentreforDiarrhoealDiseaseResearch,Bangladesh,65%ofallepisodesof
shigellosis and 80% of all deaths from shigellosis occurred in children under 5 years old (10).
Shigellosiscausesmostoftheestimated370000deathsfromdysenterythatoccurworldwideeachyear
inchildrenundertheageoffive(11).Amongchildren,theriskofdeathfromshigellosisisgreatestin
infantsandthosewhoareseverelymalnourished(12).

FourspeciesofShigellaarepathogenicforman.S.sonneiandS.boydiiusuallycauserelativelymild
illnessinwhichdiarrhoeamaybewateryorbloody(13). S.flexneri isthechiefcauseofendemic
shigellosis in developing countries, and S. dysenteriae type 1 causes both epidemic and endemic
shigellosis. Although S.dysenteriae type1isthe Shigella speciesassociatedwiththemostsevere
diseaseandthehighestcasefatalityrates,themajorityofdeathsfromshigellosisworldwideresultfrom
endemicdisease,especiallythatcausedbyS.flexneri(14).

Mostendemicshigellosisoccursinchildrenbetween6monthsand3yearsofage.Incidenceisgreatest
at the time of weaning (10,15), which is also when children are learning to crawl and walk; the
introductionofsolidfoodsandincreasedmobilityofthechildbothenhancetheriskofexposureto
faecalpathogens.Inendemicareasshigellosisisayearrounddisease,usuallypeakinginthehot,dry
season.Theincidenceofshigellosisishighestindenselypopulatedareaswithanunsafeorinsufficient
watersupplyandinadequatesanitation.Infectionisspreadbycontaminatedfoodand,lessfrequently,
bywater. Becauseaninoculumoffewerthan100organismscancauseillness,shigellosisisalso
transmittedfrompersontopersonthroughfaecalcontaminationofhands. Spreadwithinfamiliesis
common with youngchildrenusually contractingthe disease from their mothers or older siblings.
During the past 30 years large portions of Central America, South Asia and Central Africa have
experiencedepidemicsofdysenterycausedbyS.dysenteriaetype1.Thesehaveaffectedbothadults
andchildren.Inmostareastheorganismisbecomingresistanttocommonlyusedantibiotics,whichhas
madeeffectivetreatmentincreasinglydifficult(16,17).

Table1
Bacteria,otherthanShigella,thatcausebloodydiarrhoea
ininfantsandyoungchildren
Generalcomments

Diagnosis

Treatment

Campylobacter
jejuni

Causes515%ofdiarrhoeaininfantsworldwide.Indeveloping Requiresstoolculturewithspecial
countriesmostchildrenacquireimmunityduringfirstyearoflife; mediaandgrowthconditions.
pathogenfrequentlyfoundinstoolsofhealthyolderchildren.
Spreadbypoultryanddogs.

Enteroinvasive
Escherichiacoli

Uncommonindevelopingcountries.Causessporadicfoodborne Diagnosisrequiresspecialized
AntimicrobialsforShigellaprobablyeffective,
outbreaksthataffectchildrenandadults.Symptomsofillnessare techniques,including:serotyping,tissuebutefficacyhasnotbeenestablishedin
similartothoseofshigellosis.
culture,immunochemicaltestsand
controlledstudies.
DNAhybridization.

Enterohaemorrhagic
Escherichiacoli

FoundinEuropeandinpartsofNorthandSouthAmerica,where Diagnosisrequiresspecialized
AmpicillinorTMPSMX
outbreaksmaybecausedbyundercookedmeat.Recentoutbreaks techniques,including:serotyping,tissueprobablyeffectiveifagentissensitiveinvitro,
insouthernAfricatracedtoriverwatercontaminatedbycattle
culture,immunochemicaltestsand
butnocontrolledtrialshavebeendone.
carcasses.TypeO157:H7causeshaemolyticuraemicsyndrome. DNAhybridization.

Nontyphoid
Salmonella

Causes15%ofgastroenteritisinmostdevelopingcountries.
Infectionusuallyresultsfromingestionofcontaminatedanimal
products.

Conventionalculturetechniques.
Serotypingtoidentifyindividual
serotypes.

Generallycausesmildselflimitedillness.
Erythromycinandfluoroquinolonespossibly
effectiveifbegunduringfirst3daysofillness.

Antimicrobialtherapymayprolongshedding
ofthepathogeninthestool.

3.1.2Otherinvasivebacteria

Episodesofbloodydiarrhoeacausedbyotherbacterialpathogensoccurlessfrequentlythanshigellosis,
areusuallylessserious,andtheircauseisfrequentlydifficulttodetermine,exceptinhighlyspecialized
laboratories. Table1liststhesepathogens. Mostoftheseagentsrequirealargerinoculumtocause
infectionthandoShigella.Theyareusuallyspreadthroughcontaminateddrinkingwaterorfood.

3.2Entamoebahistolytica

Entamoebahistolytica isspreadbythefaecaloraltransmissionofamoebiccysts. Ingestionofcysts

mayresultininvasiveornoninvasiveinfectionofthecolon.

3.2.1Invasiveamoebiasis

Thisischaracterizedbydysentery,thepresenceinstoolspecimensoftrophozoitesof E.histolytica
containing red blood cells, characteristic pathologic lesions in the colonic mucosa, and serologic
evidenceofinfection(18).Infectionmayalsospreadtootherorgans,especiallytheliver.

InvasiveamoebiasisoccursgloballyandisanimportantpublichealthprobleminareassuchasMexico,
Guatemala,portionsofSouthAmericaandsubSaharanAfrica,andSouthAsia(18).Unlikeendemic
shigellosis,however, invasiveamoebiasisisuncommoninchildrenbelow3yearsofage,mostcases
occurringamongadults(3,8,19,20).AstudyconductedinChina,India,Mexico,MyanmarandPakistan
involving3640childrenagedunderthreeyearsofagewithacutediarrhoeayieldedonly10casesof
probableinvasiveamoebiasis(0.3%ofalldiarrhoeaepisodesandabout1.5%ofepisodesofbloody
diarrhoea),but400casesofshigellosis(whichcaused4567%ofepisodesofbloodydiarrhoea)(8).In
Bangladesh,astudyof101childrenwithbloodydiarrhoea(meanage21months)revealednonewithE.

histolyticatrophozoitesintheirstool(3).Whenamoebiasisdoesoccurinchildren,thosewithsevere
malnutritionareatgreatestriskoffataloutcome(19).

3.2.2Luminalamoebiasis

Thisreferstoasymptomatic,noninvasiveinfectionwithE.histolytica,duringwhichonlyamoebiccysts
arefoundinthestool.MostepisodesareassociatedwithnonpathogenicstrainsofE.histolyticathat
areprobablyincapableofcausinginvasivedisease(2022).Itislikelythatmostchildreninfectedwith
E.histolytica,butwithoutsymptoms,havenoninvasiveluminalamoebiasis(23).

3.3Noninfectiouscausesofbloodydiarrhoea

Bloodinthestoolcansometimesresultfrom noninfectious causes, whichmayinclude: anatomic

disorders (especially intussusception), haematological problems (such as vitamin K deficiency in
newborns),immunologicalcauses(forexample,HenochSchnleinpurpura),andulcerativecolitisor
Crohn'sdisease.Theseshouldbeconsideredwhenbloodydiarrhoeaoccursinanewborn,whensignsor
symptomssuggestingoneofthesediagnosesarepresent,orwhentreatmentofbloodydiarrhoeaforthe
usualinfectiouscausesisineffective.

4. NATURAL HISTORY OF BLOODY DIARRHOEA AND ITS RESPONSE TO

TREATMENT

4.1Shigellosis

Shigellosisinchildrenrangesinseverityfromamild,selflimitedepisodeofwaterydiarrhoeawithout
visiblefaecalbloodtofulminantdysenterythatcausesdeathinafewdays(10,24,25). Theonsetis
usuallyrapid.Insomepatientstheillnessbeginswithwaterystoolthatbecomesbloodyafteroneortwo
days.Shigellosisisoftenaccompaniedbyfeverandconstitutionalsymptoms.Bowelmovementsmay
occurveryfrequently,30timesormoreaday,andstoolsusuallycontainvisiblemucus.Asubstantial
proportion,perhaps50%,ofpatientswithdiarrhoeacausedbyShigelladonotdevelopbloodystoolsand
theirillnessisusuallymilder,resemblingacutediarrhoeacausedbynoninvasiveentericpathogens
(9,26).Infantsbelow4monthsofageareanexception:shigellosisismoresevereinthemthaninolder
childrenandhasahighercasefatalityrate;onlyabout20%,however,developbloodydiarrhoea(27).

WheninfectionwithShigellacausesdysenteryithasagreateradverseeffectonnutritionalstatusthan
doesdiarrhoeacausedbyotheragents.Thisisbecauseepisodeslastlonger(28,29),causeanorexiathat
canpersistfordaysorweeksafterrecovery(30),andmaycausesubstantiallossofserumprotein
throughdamagedbowelmucosa(16,31).Shigellosisisalsomoresevereinchildrenwithpreexisting
malnutrition,causingtheirnutritionalstatustoworsenrapidly(11,3234).

Complicationsofshigellosis,includingrectalprolapse,toxicmegacolon,bacteraemia,hyponatraemia,
hypoglycaemiaandhypoproteinaemia, occurmost frequentlyinchildrenwhoseillness isclinically
severe(31,35,36). Theriskofseverediseaseisgreatestininfants,childrenwithseveremalnutrition
(lessthan70%weightforheightorlessthan60%weightforage),childrenwhobecomedehydrated,
and children recovering from a recent episode of measles (12,27,32,37). The haemolyticuraemic
syndrome(HUS),consistingofanaemia,thrombocytopeniaandrenalfailure,iscausedbyShigatoxin
andusuallyoccursinchildreninfectedwithS.dysenteriaetype1(16).Ingeneral,complicationsare
more frequent when effective antimicrobial treatment is started more than 48 hours after onset of
symptoms.

When a child with shigellosis is given an effective oral antimicrobial, marked symptomatic
improvementwilloccurwithin48hours:therewillbelessfever,fewerstools,lessfaecalbloodandless
pain,andthechildwillresumenormalactivity(38,39). Withoutantimicrobialtreatment,orifan
ineffectiveantimicrobialisgiven,anepisodeofshigellosislastsfromtwoto10days,orlonger,andthe
riskofseriouscomplicationsordeathisgreatlyincreased,especiallyforinfectioncausedbyS.flexneri
or S.dysenteriae,type1(40). Inadequatelytreatedshigellosisisanimportantcauseofpersistent
diarrhoea(2,25,29).

4.2Bloodydiarrhoeacausedbyotherinvasivebacteria

Somefeaturesofillnesscausedbyotherimportantbacterialcausesofbloodydiarrhoeaaresummarized
inTable1.Theseagentsmayoccasionallycauseseveredisease,especiallyE.coliO157:H7,butthis
occursmuchlessfrequentlythanwithShigella.Mostcomplicationsassociatedwithsevereshigellosis
arealsounusualwiththeseinfectionsandmostepisodesimprovingspontaneouslywithintwotofive
days.Anexceptionisthehaemolyticuraemicsyndrome,whichisanimportantcomplicationofbloody
diarrhoeacausedbyE.coliO157:H7.

4.3Intestinalamoebiasis

AlthoughsymptomsofamoebiasisoverlapsignificantlythoseofdysenterycausedbyShigellaandother
invasivebacteria,amoebicdysenteryisoftengradualinonset,andpatientsmaybeillfortwoorthree
weeksbeforecomingtoahealthcentrefortreatment(19).Constitutionalsymptomsaregenerallynot
marked,andfewerthanhalfofpatientsarefebrile.Theresponseofintestinalamoebiasistoappropriate
treatmentisusuallyrapid,distinctimprovementbeingapparentwithintwotothreedays.

5.DETERMININGTHEETIOLOGYOFBLOODYDIARRHOEA

5.1Basedonclinicalfeatures

Itisnotpossiblepreciselytodeterminetheetiologyofbloodydiarrhoeainchildrenbasedonlyon
clinicalfeaturesoftheillness.Nevertheless,itisknownthatShigellacauseatleast50%ofepisodesof
bloodydiarrhoeainchildren,andnearlyallthatareclinicallysevere(8,9).Itisreasonable,therefore,
initiallytoconsider Shigella themostlikely(andmostimportant)causewheneverbloodydiarrhoea
developsinayoungchild.

5.2Basedonmicroscopicexaminationofstool

Microscopicexaminationofthestoolmaybedonetodetectpolymorphonuclearleucocytes(PMNs),
andtrophozoitesorcystsofE.histolytica.

ThepresenceofnumerousPMNsonstoolmicroscopyindicatesaninflammatoryprocessinthecolon,
usuallycausedbyinvasivebacteria,butdoesnotidentifythespecificcausativeagent.FaecalPMNsare
also found in patients with amoebic dysentery, but are usually less numerous (9,30). In general,
microscopic examination for PMNs provides little information concerning etiology that cannot be
determinedclinically.Forexample,acommunitybasedstudyofbloodydiarrhoeainBangladeshfound
thatamother'shistoryofbloodystoolswasaspredictiveofshigellosisaswasanycombinationofsigns,
symptomsandfindingsonmicroscopicexaminationofthestool(3).

A firm diagnosis of invasive amoebiasis requires the finding in fresh stool specimens of amoebic
trophozoiteswithtypicalmorphologyandcontainingingestedredcells(haematophagoustrophozoites).
However,evenexperiencedtechniciansfrequentlymistakenonpathogenicprotozoa,whitebloodcells,

macrophagescontainingredbloodcellsorpartiallydigestedvegetablematterforamoebictrophozoites
(41).Wheretheskilloftechniciansisnotconfirmedbyregularqualitycontrolprocedures,amoebiasis
isroutinelyoverdiagnosedandlaboratoryreportsareofverylittlevalue.

5.3Basedonstoolculture

Isolatinganinvasivebacterialpathogenfromstoolistheonlywaytodeterminewithcertaintythatan
episodeofbloodydiarrhoeaiscausedbyaspecificbacterialagent.However,manyinvasivebacteria
require special culture media, unusual growth conditions, or diagnostic antisera that are often
unavailableinlaboratoriesindevelopingcountries.EvenattemptstoisolateShigellamayfailunlessthe
specimenisinoculatedimmediatelyandproperlytransportedtothelaboratory.Moreover,theresultsof
cultureareavailableonlyaftertwoorthreedays,whereastreatmentmustbedecideduponwhenthe
patientisfirstseen.

6.

PRINCIPAL STEPS IN THE MANAGEMENT OF CHILDREN WITH BLOODY

DIARRHOEA

Treatmentguidelinesforbloodydiarrhoeainchildrenreflectthepointsdiscussedaboveandconsistof
thefollowingelements(alsosummarizedinFigure1):

(i)

Referimmediatelytohospitalchildrenwithbloodydiarrhoeawhoareseverelymalnourished.

(ii)

Treatandpreventdehydrationwithoralrehydrationtherapy.

(iii)

TreatallcasespromptlywithanoralantimicrobialeffectiveagainstmostlocalShigellastrains.
Giveenoughoftheantimicrobialtolastfivedays.

(iv)

Reevaluateallhighriskchildrenafter48hours. Ifthereisnotdefiniteimprovement,refer
themtohospital.

(v)

Alsoreevaluateafter48hoursallchildrenwhodonotshowdefiniteimprovement.Stopthe
firstantimicrobialandstartasecondonethatiseffectiveagainstmostlocalShigella,ifoneis
available.

(vi)

Givetherapyforamoebiasisonlywhentypicaltrophozoitesareseeninthestoolorthereisno
responsetoantimicrobialtherapyforshigellosis.

(vii)

Givefrequentsmallmealsofthechild'susualfood;continuebreastfeeding.

Duringtheclinicvisithealthstaffshouldexplaintomotherstheimportanceofantimicrobialandfluid
therapy,continuedfeedingandbreastfeeding,andadvisethemwhentoreturntothehealthcentrefor
help.

7.DETAILEDASPECTSOFCASEMANAGEMENT

7.1Detectionofbloodydiarrhoea

Thediagnosisofbloodydiarrhoeainachildismadebyaskingthemotherwhetherthechild'sstool
containsredbloodorbylookingatthestool. Thesemethodsareequallysensitiveandprecise(3).
However,askingthemotherisusuallymoreefficientthanwaitingforthechildtopassastool.

7.2Antimicrobialtherapy

7.2.1Rationale

All infants and children with bloody diarrhoea should be treated promptly with an antimicrobial
effectiveagainstShigellabecause:

(i)

bloodydiarrhoeainthisagegroupiscausedmuchmorefrequentlyby Shigella thanbyany

otherpathogen;

(ii)

shigellosisismorelikelythanothercausesofdiarrhoeatoresultincomplicationsanddeathif
effectiveantimicrobialtherapyisnotbegunpromptly;and

(iii)

earlytreatmentofshigellosiswithaneffectiveantibioticsubstantiallyreducestheriskofsevere
morbidityordeath.

7.2.2Antibioticsfor

Shigella

Unfortunately,optionsforantimicrobialtherapyofshigellosishavenarrowedconsiderablyinrecent
years as bacterial resistance has increased (Table 2). Resistance to ampicillin and cotrimoxazole,
formerlythedrugsofchoice,isnowwidespread,particularlyamongS.dysenteriae,type1,butalsoin
manyareasamongS.flexneri.Nevertheless,cotrimoxazole,andinafewareas,ampicillin,maystillbe
effectiveagainstamajorityofendemicstrains.Nalidixicacid,formerlyusedasa"backup"drugtotreat
resistant shigellosis, is now the drug of choice in many areas, but resistance to that drug is also
appearing.Healthfacilitiesinareaswherethereisahighincidenceofbloodydiarrhoeashouldtryto
stockmorethanoneantimicrobialknowntobeeffectiveagainstmostlocalstrainsofShigella.

Sometimesthereisaninsufficientsupplyofeffectiveantimicrobialstotreatallpersonswithbloody
diarrhoea. Thisismostlikelytooccurduringepidemicscausedby S.dysenteriae type1thatare
resistanttoallcommonlyavailableantimicrobials.Insuchinstancesstepsshouldbetakenurgentlyto
obtainasufficientsupplyofeffectiveantimicrobials. Untilthisisachieved,theavailablesupplyof
effectivedrugsshouldbeusedforpatientsatgreatestriskofdeath,whoare:childrenlessthanage5
years,especiallyinfantsandthosewithseveremalnutrition,adultsaged50yearsormore,andpatients
presentingwithsignsofdehydration1.

Newer drugs offering promise in the treatment of shigellosis include pivmecillinam and the new
fluoroquinolones,includingnorfloxacin,ciprofloxacinandenoxacin(40).Thenewfluoroquinolones,
whicharerelatedtonalidixicacid,arehighlyeffectiveinshigellosis,andmay

1Foradditionalinformationsee:Guidelinesforthecontrolof
epidemicsduetoShigelladysenteriaetype1,WHOdocument
WHO/CDD/93.45(Rev.1).

Table2
CurrentoptionsforantimicrobialtherapyofShigellosisindevelopingcountriesa
Drug

Costb

Availability

Resistant
organisms

Doseinchildren

Doseinadults

Ampicillin

Inexpensive

Wide

MostS.dysenteriae
25mg/kg4timesadayx5
type1;manyotherShigella days
species

Trimethoprim
Sulfamethoxazole
(TMPSMX;alsocalled
cotrimoxazole)

Inexpensive

Wide

ManyS.dysenteriaetype1; TMP5mg/kgandSMX25 TMP160mgand

variableamongotherShigella mg/kgtwiceadayx5days SMX800mgtwiceadayx5
days
species

Nalidixicacid

Inexpensive

Moderate

Increasingamong
S.dysenteriae
type1;uncommonamong
otherShigellaspecies

15mg/kg4timesadayx5
days

1g4timesadayx5days

Amdinocillin
pivoxil

Expensive

Limited

RareamongallShigella
species

20mg/kg4timesadayx5
days

400mg4timesadayx5days

Newerquinolonesd

Expensive

Moderate

RareamongallShigella
species

Notapproved

Dosagedependsonthedruge

Ceftriaxone

Expensive

Limited

RareamongallShigella
species

20mg/kgIVtwiceadayx5 1gIVonceadayx5days
days

1g4timesadayx5daysc

AdaptedfromSalam&Bennish,ref.40.
InBangladesh,forexample,theretailcostofa5daycourseoftherapyfora10kgchildisasfollows:Ampicillinsuspension,US$1.00;TMPSMXsuspension,$0.56;nalidixic
acidtablets,$0.75,andprivamdinocillincapsules,$5.63.
c
Singledosetherapyof100mg/kg,upto4g,isalsoeffectiveforchildrenabove4yearsandadults(46).
d
Thenewerquinolonesarenotyetapprovedforuseinchildrenbecausetheycausearthropathywhengiventocertainspeciesofimmaturemammals.
e
Controlledtrialsconductedinadultshavefoundthatciprofloxacin(500mgb.i.d.x5days),enoxacin(200mgb.i.d.x5days)andnorfloxacin(400mgb.i.d.x5days)areeffectivefortreatmentofshigellosis.
Ciprofloxacinhasalsobeenshowntobeeffectiveinasingledose,althoughlesssoforS.dysenteriaetype1thanotherShigella
a

proveusefulforshortcoursetherapy(42).Thesedrugsarerelativelyexpensive,however,andconcernsabouttheirsafetyinchildrenhavenotyetbeenresolved(43).Shortcourse
therapymayalsoproveeffectiveforotheragents,butfurtherresearchisneededtodeterminethis.

AntimicrobialsthatarenoteffectiveforshigellosisarelistedinTable3.TheseincludeagentstowhichShigellaareusuallyresistant.Alsolistedareagentsthatareineffective
becausetheyarepoorlyabsorbedand,therefore,donotreach Shigella thathaveinvadedtheintestinalmucosa. Treatmentofshigellosiswithanyoftheseagents,orother
antimicrobialstowhichwidespreadresistancehasdeveloped,isuselessandshouldnotbeattempted.Suchtreatmentmayalsohaveserioussideeffects.

7.2.3Antimicrobialsforbloodydiarrhoeacausedbyotherinvasivebacteria

Although illness caused by each of these agents responds to early treatment with an effective antimicrobial, this information has little practical value because appropriate
antimicrobialtherapycanbedecidedonlyafterthepathogenisisolatedbycultureanditsantimicrobialsensitivitydetermined.Forthisreason,"blind"therapywithcommonly
availableantimicrobialsisunlikelytobeeffectiveandshouldnotbegiven.

7.2.4Antimicrobialsforinvasiveamoebiasis

TherapyforamoebicdysenteryisoutlinedinTable4.Metronidazoleisthedrugofchoice.ItshouldbegivenonlywhentrophozoitesofE.histolyticacontainingredbloodcellsare
detectedinthestoolbyareliablelaboratory,orwhentwodifferentantimicrobialsusuallyeffectiveforShigellahaveprovedineffective.

Table3

AntimicrobialsthatarenoteffectiveagainstShigella

1.AntimicrobialstowhichShigellaareusuallyresistantinvitro:
Metronidazole
Streptomycin
Tetracyclines
Chloramphenicol
Sulfonamides

2.AntimicrobialstowhichShigellamaybesensitiveinvitro:
Nitrofurans(e.g.nitrofurantoin,furazolidone)
Aminoglycosides(e.g.gentamicin,kanamycin)
Firstandsecondgenerationcephalosporins(e.g.cephalexin,cefamandole)
Amoxycillin

Table4
Antimicrobialtherapyofamoebicdysentery

Antimicrobial

Metronidazole

Doseinchildren
10mg/kg3timesaday
x5days(10daysforsevere
disease)

Doseinadults
750mg3timesaday
x5days(10daysforsevere
disease)

7.2.5Misuseofmetronidazole

Metronidazole is often prescribed as initial therapy for children with bloody diarrhoea, but this is
inappropriate.Whileitremainsthedrugofchoiceforprovenamoebicdysentery,metronidazolehasno
efficacyagainstShigellaorotherinvasivebacteria2.Metronidazoleisineffectivewhengivenasinitial
therapy of bloody diarrhoea, it may have sideeffects and its use makes treatment unnecessarily
expensive.Metronidazoleisneverindicatedforchildrenwithacutewaterydiarrhoeawithoutblood.

7.3Fluids

Althoughbloodydiarrhoeaisnotusuallyassociatedwithmarkedlossoffluidandelectrolytes,the
child'sstateofhydrationshouldbeaccuratelyassessed.Ifdehydrationisdetected,itshouldbetreatedat
thehealthfacility. Childrenwithbloodydiarrhoeaandsignsofdehydrationareatincreasedriskfor
complicationsandshouldbereevaluatedafter48hoursoftreatment. Forallchildren,thecaretaker
shouldbeencouragedtoofferincreasedamountsofsuitablefluidsathome. WHOguidelinesfor
rehydrationtherapyhavebeenpublishedelsewhere(44).

7.4Feeding

Continuedprovisionofnutritiousfoodisimportantforallchildrenwithdysentery.However,owingto
anorexia,childrenmayhavetobecoaxedtoeat. Initially,childrenmayrefuseallfood,butappetite
usuallyimprovesafter2448hoursofeffectiveantibiotictherapy.Frequentsmallmealswithfamiliar
foodsareusuallybettertoleratedthanafewlargemeals.Mothersshouldbeadvisedtobreastfeedas
oftenandaslongasthechildwants.Childrenconvalescingfromdysenteryshouldbegivenanextra
mealeachdayforatleasttwoweekstohelpthemrecoverweightthatmayhavebeenlostduringthe

2Metronidazoleisalsoeffectiveforpseudomembraneousenterocolitis
causedbyC.dificile.

illness.Thecaretakersofthosewithpreexistingmalnutritionshouldbeadvisedonappropriatefeeding
practicesandthechildmonitoreduntilsubstantialweightgainhasbeendocumented.

7.5Followupandreferraltohospital

Severelymalnourishedchildrenwithbloodydiarrhoeaareatveryhighriskofcomplicationsandshould
bereferredimmediatelytohospitalafterstartingtreatmentforshigellosis. Theseincludechildren
whoseweightforageislessthan75%,orweightforlengthislessthan80%,oftheNationalCenterfor
HealthStatisticsmedians.

Allchildrenatincreasedriskofcomplicationsfromshigellosisshouldbereevaluatedafter48hours.
Theseincludethosebelow12monthsofage,childrenwhopresentwithsignsofdehydration,and
childrenwhohavehadmeaslesduringthepastsixweeks.Ifahighriskchilddoesnotshowdefinite
improvementwithin48hours,thehealthworkershouldreferthechildtothenearesthospital.

Otherchildrenwhohavenotimprovedafter48hoursshouldalsobereevaluated.Theantimicrobial
beinggivenshouldbestoppedandasecondonetowhichmostShigellaintheareaaresensitiveshould
bestarted.Ifthereisstillnoimprovementafter48hoursoftreatmentwiththesecondantimicrobial,the
drugshouldbestoppedandthechildshouldbereferredtohospitalorstartedempiricallyontherapyfor
amoebiasis.

Appropriatetreatmentofchildrenreferredtohospitalshouldbedeterminedbytheresourcesavailable
andbythefindingsonfurtherevaluationofthechild.Ataminimum,childrenshouldbeevaluatedfor:
otherinfections(suchaspneumoniaorurinarytractinfection),dehydration,malnutrition,andpossible
noninfectious causes of bloody diarrhoea. Where possible, laboratory studies should include:
microscopicexaminationofstoolforPMNs,fortrophozoitesof

E.histolytica andforotherentericparasites,andstoolculturefor Shigella andotherinvasiveenteric

bacteria,withdeterminationoftheantimicrobialsensitivityofanyisolatedpathogens.Otherimportant
studies are: complete blood count (or haematocrit), serum creatinine and urine output (to detect
haemolyticuraemicsyndrome),andserumelectrolytes(todetectserioushyponatraemia).

Managementofhospitalizedchildrenshouldfollowtheguidelinesdescribedabove,withtheadditionof
treatment for any other infections identified and appropriate dietary management of malnutrition.
Treatment for entericinfectionshould be based on laboratory findings (e.g. isolation of aspecific
bacterialpathogen,identificationoftrophozoitesofE.histolytica),butshouldnotrepeatantimicrobial
therapyalreadygiven. Whennospecificetiologicdiagnosisismade,theguidelinesgivenabovefor
antimicrobial therapy of presumedshigellosis should be followed. Patients not respondingtothis
treatmentmaybeempiricallytreatedforamoebiasis.Amoreintensivesearchfornoninfectiouscauses
ofbloodydiarrhoeashouldalsobemade.

8.OTHERMEASURES

(i) Allhealthworkersshouldbetrainedinthemanagementofbloodydiarrhoeaaspartoftheirtraining
onthecorrectmanagementofpatientswithdiarrhoea.
(ii)

Health facilities should be monitored to ensure that they are properly stocked with
antimicrobialseffectiveagainstShigellaandORSpackets,andthatcasesofbloodydiarrhoea
arerecordedinclinicrecords.

(iii)

Periodicsurveysshouldbeconductedtodeterminetheantimicrobialresistancepatternsoflocal
Shigellastrainsandtheresultsusedtorevisetreatmentguidelines,ifnecessary.

(iv)

Outbreaksofdysenteryshouldbepromptlyreportedandinvestigatedbyhealthauthoritiesto
determinetheircauseandthemostappropriatetreatment.

(v)Incountrieswhereepidemicsofbloodydiarrhoeacontributesignificantlytomorbidityandmortality

inyoungchildren,managersofnationaldiarrhoealdiseasescontrolprogrammesshouldtake
effectivestepstoreducethespreadofinfection,andpreventcomplicationsanddeaths.These
aredescribedindetailelsewhere(45).

9.ACKNOWLEDGEMENTS

DrLeilaM.Richardspreparedanearlyversionofthisdocument.Reviewersofthedocumentincluded:
Dr Michael Bennish, Tufts University School of Medicine, Boston, USA and Dr M. A. Salam,
InternationalCentreforDiarrhoealDiseaseResearch,Bangladesh,Dhaka,Bangladesh.

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