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Bloody D
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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
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
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.
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)
(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
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
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.
10. REFERENCES
1.
Victora,C.G.,Huttly,S.R.A.,Fuchs,S.C.,Barros,F.C.,Garenne,M.,Leroy,O.,Fontaine,O.,
Beau,J.P.,Faveau,V.,Chowdhury,H.R.,Yunus,M.,Chakraborty,J.,Sarder,A.M.,Kapoor,S.K.,
Bhan,M.K.,Nath,L.M.&Martines,J.C.Internationaldifferencesinclinicalpatternsofdiarrhoeal
deaths:acomparisonofchildrenfromBrazil,Senegal,BangladeshandIndia. JDiarrhoealDis
Res11:2529(1993).
2.
Black,R.E.,Brown,K.H.,Becker,S.,AbdulAlim,A.R.M.&Huq,I. Longitudinalstudiesof
infectiousdiseasesandphysicalgrowthofchildreninruralBangladesh.II.Incidenceofdiarrhea
andassociationwithknownpathogens.AmJEpidemiol115:315324(1982).
3.
Ronsmans, C., Bennish, M.L. & Wierzba, T. Diagnosis and management of dysentery by
communityhealthworkers.Lancet2:552555(1988).
4.
Briend,A.,Hasan,K.Z.,Aziz,K.M.A.&Hoque,B.A.Arediarrhoeacontrolprogrammeslikelyto
reducechildhoodmalnutrition?ObservationsfromruralBangladesh.Lancet2:31922(1989).
5.
Ronsmans,C.,Bennish,M.L.,Chakraborty,J.&Faveau,V.Currentpracticesfortreatmentof
dysenteryinruralBangladesh.RevInfectDis13(Suppl4):S351S356(1991).
6.
Hossain,M.M.,Glass,R.I.&Khan,M.R.AntibioticuseinaruralcommunityinBangladesh.IntJ
Epidemiol11:4025(1982).
7.
8.
Huilan,S.,Zhen,L.G.,Mathan,N.M.,Mathew,M.M.,Olarte,J.,Espejo,R.,KhinMaungU,
Ghafoor,M.A.,Khan,M.A.Sami,Z.&Sutton,R.Etiologyofacutediarrhoeaamongchildrenin
developing countries: a multicentre study in five countries. Bull World Health Organization
69:54955(1991).
9.
Stoll,B.J.,Glass,R.I.,HuqM.I.,Khan,M.U.,Banu,H.&Holt,J. Epidemiologicandclinical
features of patients infected with Shigella who attended a diarrhoeal diseases hospital in
Bangladesh.JInfectDis146:177183(1982).
12. Bennish,M.L.,Harris,J.R.,Wojtyniak,B.J.&Struelens,M.Deathinshigellosis:incidenceand
riskfactorsinhospitalizedpatients.JInfectDis161:500506(1990).
14. Bennish,M.L.&Wojtyniak,B.J.Mortalityduetoshigellosis:communityandhospitaldata.Rev
InfectDis13(Suppl4):S245S251(1991).
15. Ahmad, F., Clemens, J., Rao, M.R., Sack, D., Khan, M.R. & Haque, E. Communitybased
evaluationoftheeffectofbreastfeedingontheriskofmicrobiologicallyconfirmedorclinically
presumptiveshigellosisinBangladeshichildren.Pediatrics90:406411(1992).
16. Levine, M.M. Shigellosis. In: Hunter's Tropical Medicine. 7th ed. Strickland, G.T., ed.
Philadelphia:W.B.SaundersCo.,pp.340344(1991).
17. Bennish, M.L., Salam, M.A., Hossein, M.A., Myaux, J., Haque, B. & Chakraborty, J.
AntimicrobialresistanceamongShigellaisolatesinBangladesh,19831990:increasingfrequency
ofstrainsmultiplyresistanttoampicillin,trimethoprimsulfamethoxazoleandnalidixicacid.Clin
InfectDis14:10551060(1992).
18. WorldHealthOrganization.Amoebiasisanditscontrol.BullWorldHealthOrganization63:417
426(1985).
19. Wanke,C.,Butler,T.&Islam,M.Epidemiologicandclinicalfeaturesofinvasiveamoebiasisin
Bangladesh:Acasecontrolcomparisonwithotherdiarrhoealdiseasesandportmortemfindings.
AmJTropMed38:335341(1988).
22. WHO/PAHO informal consultation on intestinal protozoal infections, Mexico, 2123, October
1991.DocumentWHO/CDS/IPI/92.2.
23. Fuchs, G., RuizPalacios, G. & Pickering, L.K., Amebiasis in the pediatric population. In:
Amebiasis:HumaninfectionbyEntamoebahistolytica.RavdinJ.I.,ed.NewYork:JohnWiley&
Sons,pp.594632(1987).
24. Taylor, D.N., Bodhidatta, L. & Echeverria, P. Epidemiologic aspects of shigellosis and other
causesofdysenteryinThailand.RevInfectDis13(Suppl4):S226S230(1991).
25. Henry,F.J.Theepidemiologicimportanceofdysenteryincommunities.RevInfectDis13(Suppl
4):S238S244(1991).
26. Mathan,V.I.&Mathan,M.M.Intestinalmanifestationsofinvasivediarrhoeasandtheirdiagnosis.
RevInfectDis13(Suppl4):S311S313(1991).
27. Huskins,C.W.,Griffiths,J.K.,Faruque,A.S.G.&Bennish,M.L.Shigellosisinneonatesand
younginfants.JPediatrics(1994,inpress).
28. Black,R.E.,Brown,K.&Becker,S.Effectsofdiarrheaassociatedwithspecificenteropathogens
onthegrowthofchildreninruralBangladesh.Pediatrics73:799805(1984).
29. Lima,A.M.,Fang,G.,Schloring,,J.B.,deAlbuquerque,L.,McAuliffe,J.F.,Mota,S.,Leite,R.
&Guerrant,R.L.PersistentdiarrheainNortheastBrazil:etiologiesandinteractionswith
malnutrition.ActaPaed381(suppl):3944(1992).
30. Speelman,P.,McGlaughlin,R.,Kabir,I.&Butler,T.Differentialclinicalfeaturesandstool
findingsinshigellosisandamoebicdysentery.TransRSocTropMedHyg81:549551(1987).
31. Bennish,M.L.,Salam,M.A.,&Wahed,M.A.Entericproteinlossduringshigellosis.AmJ
Gastroenterology88:5357(1993).
32. Bennish,M.L.Potentiallylethalcomplicationsofshigellosis.RevInfectDis13(Suppl14):S319
S324(1991).
33. Chen,L.C.,Chowdhury,A.K.M.A.&Huffman,S.L.Anthropometricassessmentofenergy
proteinmalnutritionandsubsequentriskofmortalityamongpreschoolagedchildren.AmJClin
Nutr33:18361845(1980).
34. Briend,A.,Dykewicz,C.,Graven,K.,Mazumder,R.N.,Wojtyniak,B.&Bennish,M.
Usefulnessofnutritionalindicesandclassificationinpredictingdeathofmalnourishedchildren.
BrMedJ293:373375(1986).
35. Bennish,M.L.,Azad,K.M.,Rahman,O.&Phillips,R.E.Hypoglycemiaduringdiarrheain
childhood.NewEnglJMed322:13571363(1990).
36. Streulens,M.J.,Patte,D.,Kabir,I.,Salam,A.M.,Nath,S.K.&Butler,T.Shigellasepticemia:
prevalence,riskfactorsandoutcome.JInfectDis152:784790(1985).
37. Feachem,R.G.&Koblinsky,M.A.Interventionsforthecontrolofdiarrhoealdiseasesamong
youngchildren:measlesimmunization.BullWorldHealthOrganization61:641652(1983).
38. Salam,M.A.&Bennish,M.L.Therapyforshigellosis.I.Randomizeddoubleblindtrialof
nalidixicacidinchildhoodshigellosis.
JPediatrics113:901907(1988).
39. Nelson,J.D.,Kusmiesz,H.,Jackson,L.H.&Woodman,E.Trimethoprimsulfamethoxazole
therapyforshigellosis.JAmMedAssoc235:12391243(1976).
40. Salam,M.A.&Bennish,M.L.Antimicrobialtherapyforshigellosis.
JAntimicrobChemother30:243247(1992).
41. Walsh,J.A.Problemsinrecognitionanddiagnosisofamoebiasis:estimationoftheglobal
magnitudeofmorbidityandmortality.RevInfectDis8:22838(1986).
42. Bennish,M.L.,Salam,M.A.,Khan,W.A.&Khan,A.M.Treatmentofshigellosis.III.
Comparisonofoneortwodoseciprofloxacinwithstandard5daytherapy.Arandomized,
blindedtrial.AnnalsIntMed117:727734(1992).
43. Fontaine,0.Antibioticsinthemanagementofshigellosisinchildren:whatroleforthe
quinolones?RevInfectDis11(Suppl5):Sll45Sll5O(1989).
44. ProgrammefortheControlofDiarrhoealDiseases.Amanualforthetreatmentofdiarrhoea.
WorldHealthOrganization,Geneva.DocumentWHO/CDD/SER/80.2Rev.2,1990.
45. ProgrammefortheControlofDiarrhoealDiseases.Guidelinesforcontrolofepidemicsdueto
Shigelladysenteriaetype1.WorldHealthOrganization,Geneva.DocumentWHO/CDD/93.45,
1993.
46. Gilman,R.H.,Spira,W.,Rabbani,H.,Ahmed,W.,Islam,A.&Rahaman,M.M.Singledose
ampicillintherapyforsevereshigellosisinBangladesh.JInfectDis143:164169(1981).