ORIGINAL

Nigerian�Journal�of�Paediatrics�2011;38(3)120�-�124

Ugwu�GIM

Tetanus�from�IntramuscularQuinine

Injection�InWarri�NigerDelta.

Case�series:Aten�yearretrospective

study

Ugwu�EN

Received:14thMarch2011

Accepted:28thMay 2011

Summary Aim To evaluate the The case fatality rate in males is

development of tetanus from 100% but 50% in females. The

intramuscularinjectioninchildren patients were given the injections

UgwuGIM (��)

inWarri,NigerDeltaofNigeria

mainly in private clinics and the

Department�of�Paediatrics,

Delta�State�University

Teaching�Hospital,�Oghara

Nigeria

Email:gnclinic@yahoo.com

Tel:+2348026239010

Materials and Method: Retrieval remainingfromachemiststore.The

and analysis of case notes of all incubationperiodinallofthemwas

childrenwithtetanusseenbetween less than seven days. Only one of

1

999and2008atCentralHospital the patients with tetanus from

Warri with referrals from intramuscular quinine injection

surroundingGeneralHospitalsand survived,givingamortalityrateof

GN Children's Clinic one of the 80%.

fourprivatehospitalsforchildren Conclusion: Tetanus from

in Warri and its environs, and intramuscularquinineinchildrenis

noting those resulting from relatively uncommon probably

UgwuEN

ChevronWarriHospital

DeltaState,Nigeria

intramuscularinjections.

becauselessusageofthatroutefor

Results:Atotalofonehundredand quinine administration. However,

seventy five children were when it occurs, it is highly fatal.

diagnosed with tetanus with Otherroutesofparentheralquinine

twelve due to intramuscular administration such as intrarectal

injections. Out of the twelve, ten arerecommend.Thereishowevera

were from intramuscular quinine recent WHO giudelines on the

injection giving a per centage of treatment of severe falciparum

8

3.3%. Six out of the ten from malaria which showed the

intramuscularquinineweremales. superiority of intravenous

artesunateoverquinine

Introduction

portals, but for germination to occur, the bacillus

needslowoxygen-reduction(redox)potentialsuchas

Tetanusisavaccinepreventablebutnon-contagious

diseaseandisfrequentlyfatalinextremeofagesand

that associated with necrosis and proliferation is

enhancedbythepresenceofblood,foreignbodies,

andche₄micalssuchaslacticacid,calciumsaltsand

quinine�. Malaria is endemic and severe in these

developing countries and the malaria parasite has

become very resistant to various antimalarias

including chloroquine and₅ suphomethoxazole-

pyrimethamine combination. Several treatment

regimenshavebeenformulatedinvariouscountries

toovercomethisresistanceincludingintramusc₆ul₇a_,r₈,

1

in resource poor countries�. The disease has been

knownasfarbackastheperiodofearlyEgyptian

2

civilization over three thousand years ago�.It is

causedbythesecondmostpotentneurotoxincalled

tetanospasmin,whichisproducedbytheorganism

Clostridium tetanii. This is a spore-forming gram

positivestrictlyobligateanaerobe,whosesporesare

resistanttoheat,disinfectantsandotherchemicals,

andisfoundworldwide,presentinsoilandthedung

oral,andslowintravenousinfusionofquinine�,

Eachoftheseroutesofadministrationofquininehas

itsowncomplicationsandoneofthecomplications

.

3

ofsomeanimals�.Itentersthebodythroughvarious

1

21

9

of intramuscular quinine injection is tetanus�. We Whichhevomited.Hewasthenplacedon12hourly

report twelve cases of tetanus following intramuscular injection of quinine for five days. He

intramuscular injection, of which ten of the cases recoveredfromtheillness,anfivedayslaterdeveloped

followedquinineinjectioninchildreninWarriNiger generalizedspasmswithinabilitytoopenhismouth.

deltaofNigeriaoveratenyearperiodfrom1999to The spasms were unprovoked. He had two doses of

2

008.ThestudywascarriedoutatCentralHospital DTPininfancy.Hewasfoundonexaminationtobein

Warri which is the government specialist hospital, painsbutconsciouswithrhesussardonicus.Frequent

serving three local government areas with a unprovokedspasmswereobserved.Thechildwaswell

combinedpopulationoftwomillionthreehundred nourishedwithatemperatureof37.9°C.Adiagnosisof

andfiftyaccordingtothe2006Nigerianpopulation severegeneralizedtetanuswasmadewithmeningitisas

1

0

a differential. Investigations showed he had normal

bloodglucoselevelandallotherlaboratoryparameters

werenormal.

census��. The study was also carried out at GN

Children's Clinic which is one of the four private

children'shospitalsinthesamearea.

Hewasstartedon8%dextroseinfusion.Antitetanus

serum 20, 000IU was given, with 10, 000IU given

through the infusion and the other 10, 000 IU

intramuscularly.Thiswasgivenaftertestdose.Hewas

also given intravenous Ceftriazone 100mg/kg and

metronidazoleinfusion.Theantibioticwastoprocaine

penicillingivenintramuscularlyasasingledailydose.

This was after 48hours on admission. He was also

stared on intravenous diazepam .5mg/kg 6hourly,

staggered with phenobarbitone 5mg/kg 6hourly. The

sedativesweregiveninsuchawaythathereceivesa

sedativeevery3hours.Paraldehyde1ml/ageinyeartoa

maximumdoseof5mlinchildhood(hegot4ml)was

givenforbreakthroughseizures.Thespasmscontinued

and he died on the eighth day of admission despite

increasingthedoseofthediazepamandevenchanging

to chlorpromazine. Human immunoglobin was not

available

MaterialsandMethod

Retrievalofthecasenotesofallchildrenadmitted

withtetanusattheCentralHospitalWarriandGN

Children's Clinic between January 1999 and

December2008wascarriedout.Thecasenoteswere

thenanalyzed.Informationobtainedincludedamong

otherthings,theage,sexofeachpatient,presenting

symptoms,portalofentryoftheorganism,placeof

initialpresentationbeforereferraltothesecentresif

any,durationoftheillness,perinatalrecords(place

andmethodofdeliveryetc),immunizationstatusof

thechild,socialbackground(occupationofparents,

placeofdomicile,wasthechildattendingschool?

Etc), any treatment given for the illness before

presentation, past medical history, clinical signs,

managementgiventothechildreninthesehospitals

andtheoutcomeoftheillness.Followuptreatment

foreachofthepatientswasalsonoted.

Case2

This was a ten year old boy who developed fever,

vomiting,chestpainlossofappetiteandheadache.He

wastakentoachemiststorewherehewasgivendaily

quinineinjectionforsixdays,inadditiontosomeoral

tablets. He apparently recovered but one eight days

afterthelastinjections,hecomplainedofjawpainsand

adaylaterhewasunabletoopenhismouthwhichwas

Results

Oftheonehundredandseventyfivepatientsseen,

only in twelve of these children was the portal of then followed with generalized spasms. He took the

entry through intramuscular injections (6.9%). Of immunizationaccordingtoEPIschedule.Hewasfirst

thesetwelvepatients,tenwerefromintramuscular

injectionofquininegivingapercentageof83.3%

tetanus from intramuscular injection. Six of the

patientsweremales,givingamale:femaleratioof

takentoanearbyGeneralhospitalwherehestayedfor

threedaysbeforebeingreferredtoGNchildren'sclinic.

Hewasfoundonexaminationtobeconsciousinpains,

with frequent unprovoked spasms. The management

wasgenerallyalongthelineofthefirstcasebuthadto

betransfusedtwice.Healsodevelopedmeasleswhile

in the hospital and also a massive scalp sore. He

recoveredgraduallyandwasdischargedafterfiftydays

ofadmission.Atsomepointintime,theantibioticwas

changedtointravenousciprofloxacin.

3

:2.Eightoutofthepatientsdied,givingamortality

rateof80%.Oftheeightthatdied,sixweremales.So

thecasefatalityrateinmalesof100%andfemales

5

0%.wereport fivecases.

Case1

Thisisafiveyearoldboywhopresentedinaprivate

clinicwithfever, chills,vomiting,lossofappetite

andabdominalpainsHewasgivenoraldrugs,allof

REVIEW

1

22

Case3

Discussion

MasterTwasasevenandahalfyearoldboywho

developedfeverabdominalpainsandlossofappetite

andrigors.Hewastakentoaprivatehospitalwhere

he was started on 12hourly quinine injections

becausehedoesnotliketotakedrugs.Hehadthe

injectionsforfivedaysbutdevelopedunprovoked

spasmsthreedaysafterthelastquinineinjectionand

was unable to open his mouth He had the

immunizationaccordingtoEPIinahealthcentre.He

wasdiagnosedashavinggeneralizedtetanus.Hewas

treated along the line of the first patient.

Unfortunately,hediedfourdaysafteradmission.

Tetanus arising from intramuscular quinine injection

hasbeenreportedinthemedicalliteratureeveninthe

TH

11,12

earlyandmiddlepartofthe20 century, .Thoughit

can occur from intramuscular injections of other

substances, it is predominant with intramuscular

quinine.AstudyinDakarSenegalthatoutoffortysix

cases of tetanus from intramuscular injection, the

substancegivenwasidentifiableinthirtythreeofthem,

outofwhichquininewasthecauseinthirtytwoofthem

1

3

.

Thestudywasinadults.Thenumberoftwelvecases

seen here over a ten year period is relatively small

comparedtothenumberinthatstudy.Thisisprobably

because children still have some immunity from

immunization in infancy compared to adults. In our

study,theincidenceisrelativelymorecommoninthe

olderchild.ThemeanagegroupfromtheDakarstudy

Case4

She was a nine year old primary five pupil who

developedheadache,feverchillsdeepamberurine

and generalized body pain. The attending Doctor

placedheronquinineinjectionfortwodaysandoral

quinine thereafter for another five days. She

recovered and continued her studies. Seven days

after the last quinine injection, she was unable to

open her mouth which was later followed with

frequent spasms. She was first taken to the initial

doctor who diagnosed tetanus and referred her to

CentralhospitalWarri.Shewasagaintreatedalong

the line of the first patient. The frequency of the

spasms seemed to be reducing but she died two

weeksafterpresentation.

13

is34.5years.��. Moreovertheincidencemaybelower

becauseoflessuseofintramuscularquinineasopposed

tocountrieslikeVietnamandCongowhereitisamajor

14,15

formofmalariatreatment .Oneofthehypothesisfor

quinineasacauseisthatquininecausesseveretissue

necrosiswhengiventhroughthatroutewhichisagood

11 16,17

medium for the clostridia organisms, , . Infact in

tryingtoexperimentontheeffectofthetetanustoxin,

4

quininesaltsolutionisusedasasubstrate�.Quinineis

also known to potentiate the neurotoxic effects of

botilinum and tetanospasmin, the two most potent

18

neurotoxins��.

Case5

Onenotableobservationinourstudyisthattheonset

intervalformostofthepatientsislessthanoneweek.In

the study in Senegal the mean onset interval is

Hewasfiveyearsthreemonthsandfivedaysold.He

hadfeverwhichthemotherhadbeentreatingwith

various antimalaria drugs namely, chloroquine

syrup, sulphadoxine-pyrimethamine prep by roche

andhalophantrin,andwasevengivenamoxicillin-

clauvulinicacidsyrupalltonoavail.Becauseofthe

persistence of the fever, he was taken to a private

hospital where he was started on intramuscular

quinineafterlaboratorytestsshowedhehadmalaria.

Aboutthreedaysaftertheinjections,hedeveloped

generalizedbodystiffnesswithrecurrentspasms.He

wasimmunizedaccordingtotheEPIschedule.He

wasfoundtobeconsciousandcryinginpainsand

spasms observed. He was diagnosed as having

generalized tetanus and was managed generally

alongthelineofthefirstpatientbutunfortunately

diedontheseventhdayofadmission.

1

3

48hours. Mostofthepatientsaremalesandthisisthe

13,19

sameexperienceeveninadult

Themortalityinourstudyisveryhighat80%whichis

higherthantheoverallmortalityofchildhoodmortality

fromtetanuswithinthesameperiodandinthesame

2

0

studyarea��.Eventhecasefatalityismuchhigherthan

1

2

neonataltetanusinthesamearea��.Themortalityrateof

0%isclosertothatobservedinVietnamat76%but

higherthanthatrecordedintheSenegalesestudywith

2.5%. The study in Vietnam also showed the

mortalityratecomparedtotetanusfromintramuscular

8

6

1

9

injectionofotherdrugswaslowerthanwithquinine��.

The solitary patient in our study with tetanus from

intramuscularinjectionotherthanquininesurvived

The two patients with tetanus from intramuscular

injection other than quinine were female who

receivedintramuscularanlginanddiclofenacsodium

injectionrespectively,buthappily,theysurvived.

Conclusion

Quinine remains the drug of choice for treatment of

2

severemalaria��.Thehighfatalityratetetanusfromthe

1

23

World Health Organization has published a new

observedfrommanycentershasmadetheclinicians gidelineinthemanagementofseveremalariaandthe

administration of quinine intramuscularly as

1

3 15,19

recommendotherroutes��, . Someclinicians

howeverarguethatitmaybelifesavingespecially quinininefromwhateverroute.Itwasdocummented

wherevenousassessifdifficlut��.Thoughparentheral that response was better with intravenous

superiority of inravenous arthemesimin over

2

3

quinineeitherintravenouslyorintramuscularlyhas

its various complications, studies have shown that lesscombination

intrarectaladministrationofquinineisasrapidand

arthemesiminthanquininebyupto37%withmuch

25

2

4

efficacious as intravenous quinine infussion��. This

willeliminatethebiasduetodifficultyinassessing

the vein and also the risk of tetanus if given Acknowledgement

intramuscularly. A prospective study is on in our

centreontheuseofintrarectalquinine.Recently,the

We most sincerely express our gratitude to Drs

MorfonandAkposfortheirimmensehelp.

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