Prevalence of congenital malaria in high-risk Ghanaian newborns: a cross-sectional study

Enweronu-Laryea, Adjei, Mensah Benjamin, Duah Nancy, Quashie

Description

Congenital malaria is defined as malaria parasitaemia in the first week of life. The reported prevalence of congenital malaria in sub-Saharan Africa is variable (0 - 46%). Even though the clinical significance of congenital malaria parasitaemia is uncertain, anti-malarial drugs are empirically prescribed for sick newborns by frontline health care workers. Data on prevalence of congenital malaria in high-risk newborns will inform appropriate drug use and timely referral of sick newborns. Methods Blood samples of untreated newborns less than 1 week of age at the time of referral to Korle Bu Teaching hospital in Accra, Ghana during the peak malaria seasons (April to July) of 2008 and 2010 were examined for malaria parasites by, i) Giemsa-stained thick and thin blood smears for parasite count and species identification, ii) histidine-rich protein- and lactic dehydrogenase-based rapid diagnosis tests, or iii) polymerase chain reaction amplification of the merozoite surface protein 2 gene, for identification of sub-microscopic parasitaemia. Other investigations were also done as clinically indicated. Results In 2008, nine cases of Plasmodium falciparum parasitaemia were diagnosed by microscopy in 405 (2.2%) newborns. All the nine newborns had low parasite densities (≤50 per microlitre). In 2010, there was no case of parasitaemia by either microscopy or rapid diagnosis tests in 522 newborns; however, 56/467 (12%) cases of P . falciparum were detected by polymerase chain reaction. Conclusion Congenital malaria is an uncommon cause of clinical illness in high-risk untreated newborns referred to a tertiary hospital in the first week of life. Empirical anti-malarial drug treatment for sick newborns without laboratory confirmation of parasitaemia is imprudent. Early referral of sick newborns to hospitals with resources and skills for appropriate care is recommended.

Sujets

• Maladie congénitale
• Malaria
• 2008 Kosovo declaration of independence
• Ghana

Informations

• Publié par: biomed
• Publié le: 01 janvier 2013
• Nombre de lectures: 212
• Langue: English

Extrait

Enweronu-Laryea
etal.MalariaJournal
2013,
12
:17
http://www.malariajournal.com/content/12/1/17

RESEARCH

OpenAccess

Prevalenceofcongenitalmalariainhigh-risk
Ghanaiannewborns:across-sectionalstudy
ChristabelCEnweronu-Laryea
1*
,GeorgeOAdjei
2
,BenjaminMensah
3
,NancyDuah
4
andNeilsBQuashie
2

Abstract
Background:
Congenitalmalariaisdefinedasmalariaparasitaemiainthefirstweekoflife.Thereportedprevalence
ofcongenitalmalariainsub-SaharanAfricaisvariable(0-46%).Eventhoughtheclinicalsignificanceofcongenital
malariaparasitaemiaisuncertain,anti-malarialdrugsareempiricallyprescribedforsicknewbornsbyfrontlinehealth
careworkers.Dataonprevalenceofcongenitalmalariainhigh-risknewbornswillinformappropriatedruguseand
timelyreferralofsicknewborns.
Methods:
Bloodsamplesofuntreatednewbornslessthan1weekofageatthetimeofreferraltoKorleBu
TeachinghospitalinAccra,Ghanaduringthepeakmalariaseasons(ApriltoJuly)of2008and2010wereexamined
formalariaparasitesby,i)Giemsa-stainedthickandthinbloodsmearsforparasitecountandspeciesidentification,
ii)histidine-richprotein-andlacticdehydrogenase-basedrapiddiagnosistests,oriii)polymerasechainreaction
amplificationofthemerozoitesurfaceprotein2gene,foridentificationofsub-microscopicparasitaemia.Other
investigationswerealsodoneasclinicallyindicated.
Results:
In2008,ninecasesof
Plasmodiumfalciparum
parasitaemiawerediagnosedbymicroscopyin405(2.2%)
newborns.Alltheninenewbornshadlowparasitedensities(
≤
50permicrolitre).In2010,therewasnocaseof
parasitaemiabyeithermicroscopyorrapiddiagnosistestsin522newborns;however,56/467(12%)casesof
P
.
falciparum
weredetectedbypolymerasechainreaction.
Conclusion:
Congenitalmalariaisanuncommoncauseofclinicalillnessinhigh-riskuntreatednewbornsreferred
toatertiaryhospitalinthefirstweekoflife.Empiricalanti-malarialdrugtreatmentforsicknewbornswithout
laboratoryconfirmationofparasitaemiaisimprudent.Earlyreferralofsicknewbornstohospitalswithresources
andskillsforappropriatecareisrecommended.
Keywords:
Congenital,Malaria,Newborn,Ghana

Background
Congenitalmalaria,definedasmalariaparasitaemiain
Malariainpregnancyisamajorunderlyingcauseofneo-thefirstweekoflifecanbeacquiredtransplacentallyor
natalmorbidityinendemicregions[1-3].Theburdenofduringthetimeofbirth.Theprevalenceinsub-Saharan
malariainpregnancyishighestinsub-SaharanAfricaAfricahasbeenreportedtovaryfrom0
–
46%[7];how-
where1:4pregnantwomenhaveevidenceofplacentalin-ever,morerecentmulticentrelongitudinalstudieshave
fectionatthetimeofdelivery[4-6].Pregnancyassociatedreportedlowerratesof4
–
6%[8,9].Clinicalmalariaisrare
malariahasbeenimplicatedasacauseofstillbirths,pre-innewbornsfromendemicareaswithhighincidenceof
maturebirths,intrauterinegrowthrestrictionandconse-malariainpregnancy.Thisrareoccurrencehasbeenattrib-
quentlylowbirthweight(LBW)inaffectednewborns.utedtothetransplacentaltransferofmaternallyderived
However,itseffectasacauseofclinicaldiseaseintheantibodiestomalaria,andtheinhibitoryeffectoffoetal
newbornespeciallyinthefirstweekoflife,whenmosthaemoglobinonmalariaparasitedevelopment[10-12].
newbornillnessesanddeathsoccur,isuncertain.Theprevalenceofcongenitalmalariainacommunity
basedprospectivestudyininfantsinsouthernGhana
*
1
Correspondence:[e-mail]
in1998was13.6%bypolymerasechainreaction(PCR)
DepartmentofChildHealth,UniversityofGhanaMedicalSchool,POBox
and2.5%bymicroscopy[13].Inthatstudytheriskof
4236,Accra,Ghana
Fulllistofauthorinformationisavailableattheendofthearticle
©2013Enweronu-Laryeaetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsofthe
CreativeCommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,
distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Enweronu-Laryea
etal.MalariaJournal
2013,
12
:17
http://www.malariajournal.com/content/12/1/17

infectionwasthreetimeshigherduringtherainyseason
(April
–
July)ascomparedtothedryseason.Recently,
twocasesofsymptomaticcongenitalmalariawere
reportedinGhanaiannewborns[14,15].
Clinicalmalariainthenewbornusuallymanifestsafter
thefirstweekoflife(buthasbeenreportedonday1)with
symptomssuchasfever,poorfeeding,lethargy,anaemia,
hepatosplenomegaly,jaundice,irritability,anddrowsiness.
Theseclinicalfeaturesaresimilartothemanifestationsof
neonatalsepsisandotherneonatalconditionsthatmore
commonlycausemorbidityandmortalityinthenewborn
period[8,16,17].Manymalariaendemicsub-Saharan
Africancountrieslackqualitylaboratoryequipmentand
skilledfrontlinehealthcareworkersinprimaryhealthcare
facilities.Assuch,diagnosingneonatalproblemsisamajor
challengeandempiricaltreatmentformalariaisoften
prescribedwhennewbornsfirstpresentwiththeabove
symptoms.Sicknewbornsarereferredtohospitalfewdays
laterwhenmalariatreatmentdoesnotresolvesymptoms.
Thispracticeresultsindelayedreferralofsicknewborns
forappropriatecareandcontributestothehighneonatal
mortalityandlong-termmorbidityinsurvivorsinthesub-
region.
MalariaisendemicinGhanaandWorldHealth
Organization(WHO)guidelinesforempiricaltreatment
ofmalariainsuspectedcasesiswidelyadheredto[18].
Thispracticeisextendedtosicknewbornsbyprimary
carehealthworkerscontrarytoexistingguidelineson
theIntegratedManagementofChildhoodIllnesses.
Thoughmanyunderlyingreasonsmayaccountforthis
practiceinsicknewborns,thelackofsufficientlocal
dataoncongenitalmalariamaybeacontributoryfactor.
Thisstudypresentstheprevalenceofmalariaparasit-
aemiainnon-treatedhigh-risknewbornsreferredtoa
teachinghospitalinthefirstweekoflife.
Methods
Thiscross-sectionalstudywasdoneatthenewbornunit
andmalariaresearchlaboratoryoftheDepartmentof
ChildHealth,KorleBuTeachingHospital,inAccradur-
ingthepeakmalariaseasons(April
–
July)of2008and
2010.The55-bednewbornunitservesasatertiaryrefer-
ralcentreforsickandlowbirthweightorpretermnew-
bornsfromsouthernregionsofGhana.About2000
newbornsareadmittedannually.Ethicalapprovalwas
givenbytheEthicalandProtocolReviewCommitteeof
theUniversityofGhanaMedicalSchool.
Allnewbornshospitalizedatthenewbornunitinthe
firstweekoflifeduringthestudyperiodwereeligible
forinclusion.Newbornswithclinicalindicationsthat
requiredbloodsamplinge.g.signsofillnessorriskfac-
torsforinfectionwereenrolled.Stablenewbornse.g.
infantsofdiabeticmothersorwellpreterminfantsof
hypertensivemotherswhowerereferredforobservation

Page2of5

anddidnotrequirelaboratoryinvestigations,were
excluded.Allclinicalproceduresandlaboratoryinvesti-
gationsforhospitalizednewbornsweredoneaccording
tostandardanddepartmentalguidelines.
Astructuredquestionnairewasusedtocollectclinical
dataonnewbornandmaternalhealthduringpregnancy,
includinguseofinsecticidetreatednetsandintermittent
preventivetreatment.Otherclinicaldatawasextracted
fromthewardregisterandhospitalfiles.Samplesize
calculationwasbasedonanestimatedprevalenceofa
20%riskofcongenitalmalariainhigh-risknewbornsin
thefirstweekoflife[2,11].
Laboratoryinvestigations
Newbornvenousblood(1ml)wascollectedintoEDTA
tubesforhaematologicalinvestigations.Totalwhiteblood
cellcount(WBC)withdifferential,plateletcountandred
celldistributionwidthwasmeasuredbyanautomated
haematologyanalyzer(SysmexKX-21)accordingtoman-
ufacturer
’
sinstructions.Thickandthinbloodsmearspre-
paredfromtheEDTAsamplewerestainedwithGiemsa.
Thinsmearswereusedformalariaparasitespeciesidenti-
fication,andthenumberofasexualparasitesper200
whitebloodcells(WBC)onthethicksmearwasmulti-
pliedbythemeasuredWBCcounttoobtaintheparasite
countpermicrolitre.Anexperiencedtechnologistcon-
ductedperiodiccontrolsofbloodslidesforqualitycontrol.
Thistraditionalmethodofmicroscopywasusedin2008
and2010.In2010,arapiddiagnosistest(RDT)foridenti-
ficationofmalariaparasitehistidinerichprotein2andlac-
tatedehydrogenase(theFirstResponse
W
malariaantigen
pLDH/HRP2ComboTest),andanestedPCRmethods
wereusedtoidentifysub-microscopicparasitaemia.
TRDWTheFirstResponsemalariaantigenpLDH/HRP2
ComboTest(PremierMedicalCorporationLtd,India)is
designedforthedifferentialdiagnosisbetween
Plasmo-
diumfalciparum
andotherplasmodialspecies.Itcon-
tainsamembranestrippre-coatedwithtwomonoclonal
antibodiesastwoseparatelinesacrossateststrip.One
monoclonalantibodyispan-specifictolactatedehydro-
genaseofthePlasmodiumspeciesandtheothermono-
clonalantibodyisspecifictohistidine-richprotein2of
P.falciparum
[19].
PRCThiswasdoneattheNoguchiMemorialInstitutefor
MedicalResearch,UniversityofGhana.ParasiteDNA
wasextractedfromwholebloodsamplesspottedonfil-
terpaper,usingtheTEmethod[20].AnestedPCR
methodforamplificationofthemerozoiteprotein2
(MSP)genewasusedforthedetectionof
P.falciparum
.
Theprimaryamplificationreactioninvolvedtheuseof

Enweronu-Laryea
etal.MalariaJournal
2013,
12
:17
http://www.malariajournal.com/content/12/1/17

theprimerpair,S2(5
’
-5
’
GAGGGATGTTGCTGC
TCCACAG3
’
)fora450-800basepairproduct.The
PCRproductobtainedwasusedasthetemplateforthe
secondaryPCRusingthefollowingprimerpairs:S1(5
’
-
GAGTATAAGGAGAAGTATG-3
’
)andS4(5
’
-CTA