Infectious
disease
exposures
and
outbreaks
at
a
South
African
neonatal
unit
with
review
of
neonatal
outbreak
epidemiology
in
Africa
A.
Dramowski
a,*
,
M.
Aucamp
b,
A.
Bekker
a,
S.
Mehtar
ba
DepartmentofPaediatricsandChildHealth,FacultyofMedicineandHealthSciences,StellenboschUniversity,POBox241,CapeTown8000,SouthAfrica
b
AcademicUnitforInfectionPreventionandControl,DivisionofCommunityHealth,FacultyofMedicineandHealthSciences,StellenboschUniversity,Cape Town,SouthAfrica
ARTICLE INFO Articlehistory:
Received30November2016
Receivedinrevisedform17January2017 Accepted23January2017
CorrespondingEditor:EskildPetersen, Aar-hus,Denmark Keywords: Neonates Africa Outbreaks Nosocomial Infectionprevention SUMMARY
Background:Hospitalizedneonatesarevulnerabletoinfection,withpathogenexposuresoccurringin utero, intrapartum,and postnatally.Africanneonatal unitsare athigh risk ofoutbreaks owingto overcrowding,understaffing,andsharedequipment.
Methods:Neonataloutbreaksattendedbythepaediatricinfectiousdiseasesandinfectionprevention(IP) teamsatTygerbergChildren’sHospital,CapeTown(May1,2008 toApril30,2016)aredescribed, pathogens,outbreaksize,mortality,source,andoutbreakcontrolmeasures.Neonataloutbreaksreported fromAfrica(January1,1996toJanuary1,2016)werereviewedtocontextualizetheauthors’experience withinthepublishedliteraturefromtheregion.
Results:Thirteenoutbreaksaffecting148babies(11deaths;7%mortality)overan8-yearperiodwere documented,withpathogensincludingrotavirus,influenzavirus,measlesvirus,andmultidrug-resistant bacteria(Serratiamarcescens,Acinetobacterbaumannii,methicillin-resistantStaphylococcusaureus,and vancomycin-resistantenterococci).Althoughtheinfectionsourcewasseldomidentified,mostoutbreaks wereassociatedwithbreachesinIPpractices.Stringenttransmission-basedprecautions,staff/parent education, and changes to clinical practices contained the outbreaks. From the African neonatal literature, 20 outbreaks affecting 524 babies (177deaths; 34%mortality) wereidentified; 50% of outbreakswerecausedbyextended-spectrumb-lactamase-producingKlebsiellapneumoniae. Conclusions:OutbreaksinhospitalizedAfricanneonatesarefrequentbutunder-reported,withhigh mortality and a predominance of Gram-negative bacteria. Breaches in IP practice are commonly implicated,withtheoutbreaksourceconfirmedinlessthan50%ofcases.ProgrammestoimproveIP practiceandaddressantimicrobialresistanceinAfricanneonatalunitsareurgentlyrequired. ©2017TheAuthor(s).PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases. ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(
http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Hospitalizedneonates area vulnerable populationowing to immature immunity and frequent infectious disease exposures through contact with healthcare staff, parents, other patients, equipment,andthehospitalenvironment.Exposureeventsmay leadtomicrobialcolonizationorinfectionwithseveremorbidity and mortality, as well as nosocomial outbreaks. Outbreaks in neonatalunits(NNUs)ofhigh-incomecountriesoccuratarateof 10peryear.1ThefrequencyofoutbreaksintheNNUsoflow-and middle-incomecountries(LMICs)isunknown,butislikelytobefar
higherowingtoovercrowding,understaffing,andthesharingand reuseofequipment.2Despitetheseriskfactors,publishedoutbreak reportsfromAfricanNNUsareinfrequentandhinderedbylimited microbiology laboratory access and an absence of healthcare-associatedinfection(HAI)surveillanceprogrammesandinfection prevention(IP)resources.2
Point prevalence studies in high-income countries report healthcare-associated neonatal bloodstream infection (HA-BSI) as themost frequent infectiontype affecting hospitalized neo-nates,3 althoughviralrespiratoryandgastrointestinalinfections arealsoencountered.GiventhehighratesofHA-BSIreportedfrom some African settings,4–6 frequent outbreaks of nosocomial bacterialinfectioncouldbeexpectedinAfricanNNUs.Thelimited African neonatal HA-BSI descriptions reflect a predominance
of Gram-negative pathogens and substantial antimicrobial
* Correspondingauthor.Fax:+27219389138. E-mailaddress:dramowski@sun.ac.za(A. Dramowski).
http://dx.doi.org/10.1016/j.ijid.2017.01.026
1201-9712/©2017TheAuthor(s).PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
ContentslistsavailableatScienceDirect
International
Journal
of
Infectious
Diseases
resistance.4–6Arecentsystematicreviewof30neonataloutbreaks (2005–2015), identified Klebsiella pneumoniae (33%), Serratia marcescens(20%),andmethicillin-resistantStaphylococcusaureus
(MRSA) (20%) as the most common pathogens.7 The mean
outbreakdurationwas10monthsandtheoutbreaksourcewas identifiedin17/30cases(57%):neonatestransferred-infromother facilities(n=6),contaminatedventilatorequipment(n=5), health-careworkers(n=4), and colonized mothers(n=2). Thelack of resourcesforoutbreakinvestigation(includinglaboratoryservices and molecular testing), hampers efforts to identify outbreak frequencyandsourceinAfricanNNUs.7
ReportedNNUoutbreakmortalityratesarehigh,withtherisk ofdeathinverselyproportional tothecountryincomelevel(9–
70%).7 The highest mortality rates are documented among
neonates with laboratory-confirmed Gram-negative and fungal BSIpathogens.4,6,7Alackofneonatalintensivecareunits(NICUs) and limited access to appropriate treatment for antimicrobial-resistantinfectionscontributetoincreasedmortalityinLMICNNU outbreaks.
This article describes the Tygerberg Children’s Hospital experience with the detection, investigation, and control of outbreaks in the NNU since 2008, in the contextof published outbreak reports from other African NNUs over the last two decades.
Methods Studysetting
TygerbergChildren’sHospitalinCapeTown,SouthAfricaisa 124-bed neonatal referral centre located within a 1384-bed tertiary government hospital. The NNU provides medical and surgical care for sick and/or low birth weight (LBW, <2500g) neonates, with prematurity, perinatal asphyxia, and neonatal sepsis beingthe predominant reasons for admission. The NNU consistsofaneight-bedNICU(combinedsurgicalandmedical),a four-bedhigh-care,twohigh-carewards,onelow-careward,anda kangaroomothercareunit.BedoccupancyratesintheNNUrange from83%to138%,withahighdemandforNICUbeds.Thehospital performsaround8000neonataldeliveriesannually,withaLBW rateof39%.Motherswithcomplicatedpregnanciesarereferredin fromthesurroundingsocioeconomicallydeprivedcommunities.8 In the Western Cape Province, antenatal HIV prevalence increased between 2009 and 2013, from 16.1% to 16.9% (vs. 29.5%nationally).9Combinationantiretroviraltherapy(cART)has been available since 2004, with universal cART in pregnancy (irrespective of CD4 count) introduced from 2013. Between 2009 and 2011, a national prevention of mother-to-child HIV infectiontransmission(PMTCT)programmeachievedareduction intheWesternCapeProvinceperinatalHIVtransmissionratefrom 3.6%to1.4%.8,10
Studyperiodandmethod
Data on NNU outbreaks investigated by the infection
prevention service and/or the paediatric infectious diseases team betweenMay 1, 2008 andApril 30, 2016were collected
prospectively. An outbreak was defined as any infectious
disease (ID) cluster affecting two or more babies with the same pathogen within 7days (isolated from sterile sites, with thesameantibiogramforbacterialpathogens),orisolationofa singleunusualorimportantpathogen,e.g.,measles,Pseudomonas spp.11 For each outbreak, the pathogen, NNU ward/s affected, numberofcasesand casefatalityrate,thepresumedorknown source,andtheIPmeasuresinstitutedforoutbreakcontrolwere documented.
Investigationforsuspectedneonatalsepsis
Sickneonateswithanyclinical,radiological,and/orlaboratory featuressuggestinginfectionundergoatleastonebloodculture with/withoutaccompanyingcerebrospinalfluidandurineculture specimens,atthediscretionoftheattendingclinicians.Symptoms and signs that trigger investigation for sepsis include lethargy, apnoea, need for increased respiratory support, poor feeding, temperatureinstability, abdominaldistension, and raisedwhite cell countor C-reactiveprotein, among others. Given the high prevalenceofextended-spectrum
b
-lactamase(ESBL)-producing Enterobacteriaceaeatthestudyinstitution,theempiricaltreatment of hospital-acquired infection usually includes meropenem. Vancomycin is added ifMRSA is considereda likely pathogen, e.g.,withsuspectedcentrallineorsofttissueinfection.Fluconazole prophylaxisisnotroutinelyused.Investigationforpotentialviral pathogens is undertaken based on clinical presentation, e.g., gastroenteritis (rotavirus and adenovirus) and respiratory tract infection (respiratory syncytial virus (RSV), adenovirus, human rhinovirus, parainfluenza virus 1/2/3, influenza virus A/B, and humanmetapneumovirus)usingrapidassays,ELISA,orPCRpanel testing.Outbreaksurveillance,investigation,andmanagement
Thehospitalhasanon-siteunitforinfectionpreventionand control(UIPC)thatconductslaboratorysurveillanceforselected bacterial ‘alert’ pathogens: K. pneumoniae, MRSA, Enterobacter cloacae,Pseudomonasaeruginosa,S.marcescens,andAcinetobacter baumannii). Clinician reports of infection clusters are also an important trigger for outbreak investigation. Four IP nurse practitioners are employed (ratio 1:350 patients), with one dedicatedtotheneonatal,paediatric,andmaternityservice.Most infectionclustersandoutbreakalertsareinitiallyinvestigatedby line-listingofaffectedpatientsandareviewofIPpracticesonthe NNU. The detection of additional related cases results in an outbreakbeingofficiallydeclaredwiththeassemblyofanoutbreak team,institutionofIPmeasuresbasedonthesuspectedsourceand routeoftransmission,andfurtherepidemiologicalinvestigations wherenecessary.Institutionalchangesthatmayhaveinfluenced NNUinfectionratesandoutbreakfrequencyincludethe installa-tionofautomatedalcoholhand-rubdispensers(in2013)andthe introductionofacentralline-associatedBSI(CLABSI)programme intheNICU(in2012).Otherthanincreasingadmissionvolumes andongoingstaffshortages,therewerenosignificantchangesin patientprofileorphysicianpracticesduringthestudyperiod. Literaturesearchterms
PubMed, Scopus, and the online outbreak database http:// www.outbreak-database.com were searched using the terms “neonate”, “Africa”, “nosocomial”, “healthcare-associated infec-tion”,and“outbreaks”forEnglish-languagepaperspublishedfrom January1,1996toJanuary1,2016.Eachpublicationoroutbreak databaserecordwasreviewedtoextractthefollowinginformation (when available): year of outbreak, country, neonatal setting, pathogen, number of clinical cases, deaths reported, presumed sourceorfactorsimplicatedintheevolutionoftheoutbreak,andIP measuresimplementedforoutbreakcontrol.
Results
Overthe8 years,TygerbergChildren’sHospitalNNU experi-enced 13 outbreaks affecting 148 babies with 11 deaths (7% mortality)(Table1).Multidrug-resistantbacteriawerethemost frequent pathogens, followed by outbreaks of viral diseases
introducedintotheNNUduringlarge-scalecommunityoutbreaks. Twoseparaterotavirusoutbreaks(involving58and16neonates, respectively)occurredin 2008and 2010,affecting theneonatal wardsand theNICU.Theoutbreak wasinvestigatedusing line-listing,Ganttcharts,weeklyepidemiologicalcurves,and submis-sionofstoolrotavirusenzymeimmunosorbentrapidassaysfrom symptomaticneonatesandmothers.Containmentmeasuresinthe firstoutbreak included temporary ward closures,preventionof transfers betweenwards, and cohort isolation of neonates (in incubators)oncontactanddropletprecautions.Mothersandstaff wereeducated ontheneedfor compliancewithhand hygiene, precautions, and careful disposal of baby nappies, and daily symptomscreening ofmothersfor gastroenteritis identifiedsix incident cases of maternal transmission (confirmed on stool enzymeimmunoassay(EIA)). Rotavirus‘exposed’babies(in the
same room as infected babies) were screened by EIA if
symptomaticand observedforat least72hbeforetransferout. Thesecondoutbreakwasfarsmallerandmorerapidlycontrolled (in 6 vs.12 weeks) without any ward closures, owing to staff familiarityandbettercompliancewiththerotavirusmanagement protocolestablishedinthe2008outbreak.
The 2009 H1N1 influenza pandemic infected approximately 12000SouthAfricanswith91reporteddeaths.12Pregnantwomen wereespeciallyseverelyaffected,withtheICUcapacitytoventilate
critically ill pregnant women at Tygerberg Hospital rapidly exceeded.13 Nosocomial transmission of H1N1 influenza was confirmed in fiveneonates (three mothers and one healthcare worker testedpositive forH1N1), witha furtherfour‘exposed’ babies. The five infected babies had a median hospital stay of 20daysatthetimeoflaboratorytesting,withamediangestational age of 28 weeks and weight of 1130g; all were treated with oseltamivir and requiredNICU admission. One prematurebaby diedfromnecrotizingenterocolitis(NEC)3daysaftercompletion of oseltamivir therapy.14 Droplet precautions, cough etiquette, hand hygiene compliance, cohort isolation of infected/exposed babies, visitor restriction, and exclusion of symptomatic staff memberswasinstituted.Theoutbreakhighlightedashortageof patientisolationfacilities,particularlyintheNICU,andreinforced theimportanceofannualstaffinfluenzavaccination.
During acountry-widemeaslesoutbreak in2009/2010,with over 30000 confirmed cases nationally, a case of congenital measleswasidentifiedonaneonatalward.A33-weekgestation neonate developed a maculopapular rashon day4 of life. The historyofmaternalillnesshadnotbeenavailableatthetimeanda differentialdiagnosisofenteroviralinfection,phototherapyrash, andcongenitalmeasleswasconsidered.Urineandathroatswab werepositiveformeaslesonPCR;subsequentlymeaslesserology wasIgM-positiveforthemotherandbaby.ImmediateIPmeasures
Table1
OutbreaksaffectingtheTygerbergHospitalneonatalunit(May1,2008toApril30,2016). Outbreak
year/s
Setting Pathogen Casesa
(n)
Deaths (n)
Presumedorconfirmedoutbreak source
IPmeasuresforoutbreakcontrol
2008 NNU Rotavirus 58 0 Presumedintroductionbyan
infectedmotherorhealthcare worker
HH,CP,DP,temporaryWC,VR,openingofadditionalNICUspace forpatientisolation,cohortisolationinincubators,careful disposalofbabynappies,enhancedenvironmentalandequipment cleaning,educationofstaffandparents,dailyscreeningofmothers forsymptomsofgastroenteritis(6identified)
2009 NNU H1N1influenza
virus
5 1 Presumedintroductionbyan infectedmotherorhealthcare worker
HH,DP,cohortisolation,educationofstaffandparents,VR, exclusionofsymptomaticstaffmembers
2010 Wards Rotavirus 16 0 Presumedintroductionbyan
infectedmotherorhealthcare worker
CP,DP,HH,VR,noWC,cohortisolationinincubators,enhanced environmentalcleaning,attentiontohandlingofnappies,staffand parenteducation
2010 Ward Measlesvirus (congenital)
1 0 Measles-infectedmotherduringa country-widemeaslesoutbreak
AP,cohortisolationofcaseand‘contacts’inincubators,designated staffingtotheaffectedcubicle,immunoglobulintoexposed babies,measlesvaccinetonon-immuneadults
2012 NNU Serratiamarcescens 12 4 Reusedandinadequately decontaminatedventilatortubing
Thepracticeofreusingventilatortubingwasstopped,hospital managementapprovedfinancialexpenditureforpurchasingnew tubing,afaultywasher-disinfectorwascondemnedandreplaced, sterileservicesstaffwereretrainedondisinfectionmethods
2012–13 NNU MRSA 24 0 Nosourceidentified,ascribedto
non-compliancewithbasicIP measures
CP,HH,staffeducation,MRSAdecolonizationprotocolfor colonizedandinfectedstaffandneonates(chlorhexidine gluconatebodywashes+mupirocinintranasalointment7days), enhancedenvironmentalcleaning
2013 NNU MRSA 3 0 Nosourceidentified CP,HH,staffeducation,cohortisolation,MRSAdecolonizationof casesand‘contacts’inthesamecubicles
2013 NICU VRE 2 0 Nosourceidentified CP,HH,cohortisolation,movementofneonateswithinthe affectedwardswaslimited,enhancedenvironmentalcleaning, staffeducation
2014 NNU MRSA 4 0 Nosourceidentified,ascribedto
non-compliancewithbasicIP measures
CP,HH,VR,staffeducation,cohortisolation,partialWC(affected cubicleswereclosedtonewadmissions),MRSAdecolonization, enhancedenvironmentalcleaning
2014 NICU VRE 1 0 Nosourceidentified CP,HH,cohortisolation,temporaryWCoftheaffectedNICU cubicle,enhancedenvironmentalcleaning
2014 NICU Acinetobacter baumannii
4 2 Nosourceidentified CP,HH,cohortisolation,aseptictechniqueforinsertionand maintenanceofindwellingdevices,enhancedenvironmentaland equipmentcleaning
2015 NNU MRSA 4 0 Nosourceidentified CP,HH,MRSAdecolonization,cohortisolation,enhanced environmentalcleaning
2015 NNU Serratiamarcescens 10 4 Nosourceidentified CP,HH,introducedeyecareprotocols,emphasizedaseptic techniqueforprocedures,newcleaningprotocolsforshared equipment,enhancedfrequencyofenvironmentalcleaning AP,airborneprecautions;CP,contactprecautions;DP,dropletprecautions;ESBL,extended-spectrumb-lactamaseproducer;HH,intensifiedhandhygiene;IP,infection prevention;MRSA,methicillin-resistantStaphylococcusaureus;NICU,neonatalintensivecareunit;NNU,neonatalunit;VR,visitorrestriction;VRE,vancomycin-resistant Enterococcus;WC,wardclosure.
a
implemented were airborne precautions, cohort isolation, and designatedstaffingtotheaffectedneonatalcubicle. Immunoglob-ulin(Intragam)wasgiventoexposedbabiesandmeaslesvaccine wasprovidedtonon-immunehealthcareworkersandparents.
OftheninebacterialoutbreaksincludingS.marcescens(n=2),A. baumannii(n=1),MRSA(n=4),andvancomycin-resistant Entero-coccusfaecium(VRE;n=2),onlyonehaddefinitiveidentificationof theoutbreak source.AnS.marcescensoutbreakthat affected12 prematureneonates(withfourdeaths)betweenJulyandOctober 2012was ascribedtothereuseand inadequatereprocessingof ventilatortubing.Theoutbreakinvestigationincludedrapidcase identificationwithline-listing(revealingthat11/12caseshadbeen ventilated) and cultures of potential sources (used and re-processed,re-packaged‘clean’ventilatorcircuits).Clinicalisolates andS.marcescensisolatedfromventilatortubingweregenotyped usingpulsed-fieldgelelectrophoresis(PFGE)identifyingasingle majorclone.Transitiontosingle-useventilatorcircuits,heightened handhygienecompliance,andenhancedenvironmentalcleaning terminatedtheoutbreak.
ThefirstNNUoutbreaksofVREoccurredin2013and2014.VRE wasisolatedfromtwoNICUpatients(fromatissuespecimenafter surgeryforNECinonecaseandfrombloodcultureintheother). TwofurtherNICUpatientsgrewVREfromcatheter tipsbutnot fromperipheral blood cultures. The outbreak measures imple-mentedincludedtheformationofanoutbreakteam,screeningof patientsintheNICU,contactprecautionsandcohortisolationof casesandcolonizedpatients,enhanced environmentalcleaning, limiting of patient transfers, and staff/parent education with emphasis on hand hygiene. Targeted active screening for VRE colonizationwasinitiallyconductedon19infants(16%carriage prevalence) and a month later on 12 infants (67% carriage), includingfiveinitiallyVREscreen-negativeneonateswhobecame newlycolonized,suggestingabreakdownintransmission-based precautions. One infected baby remained VRE colonized for 9monthsaftertheoutbreak.Noneoftheenvironmentalscreening swabs(n=14)cultured VRE.The vanA genewas detected inall clinicalisolatesandPFGEanalysisdistinguishedninepulsotypes withonepredominantclone.In2014,VREwasre-introducedinto theNICUthroughtransfer-inofaprematureinfantwithNECand ilealperforationfromanotherhospital.Fourcontacts(babiesinthe sameICUroom) werescreened(allnegative) andkeptonstrict contactprecautions;theaffectedICUcubiclewasclosedtonew admissions.Isolationprecautions werequickly and successfully implementedgiven staff familiaritywith theIP measuresused duringthepreviousoutbreak.
Four outbreaks of MRSA occurred between 2012 and 2015, affecting24neonatesin2012/13and11babiesinthesubsequent threeoutbreaks,withnodeaths.The2012/13outbreakincluded MRSA BSI (n=13), conjunctivitis, and skin and soft tissue infections,whichoccurredovera 16-weekperiodwithongoing MRSAcolonizationbetweenclusters.ScreeningidentifiedMRSA carriagein16/140babiesintheneonatalunit(11%).Staffscreening wasperformedfromoutbreakweek8becauseofongoingMRSA transmission,witha1%positivityrate(2/208).Staffscreeningwas very unpopular, labour-intensive, and costly, with a low yield. MotherswerenotscreenedforMRSAcarriage(largelyowingto cost implicationsand thelower risk of transmission,since the mothersonlycaredfor theirownbabiesand werediscouraged fromtouchingotherbabies).IPmeasuresimplementedincluded contactprecautions,staffeducation,andMRSAdecolonizationof infected/colonizedneonatesandstaffwithchlorhexidine gluco-natebodywashesandmupirocinintranasalointmentfor7days. Thepharmacystaffwereparticularlyconcernedabouttopicaluse of chlorhexidine gluconate in neonates (particularly in LBW babies).Asacompromise,dailywasheswith0.25%chlorhexidine gluconatewereused,withnoadverseeventsreportedamongthe
24 infected and 16 colonized babies. In subsequent MRSA
outbreaks,earlyidentificationofcasesandprompt implementa-tion of isolation measures helped to restrict the size of the outbreaks.
In2015,fourneonatesintheNICUdevelopedA.baumannii HA-BSI (twobabies died).The outbreak investigation utilized line-listingand observation of clinicalpractices in theNICU, noting severe shortages in clinical and support staff preceding the outbreak.IPmeasuresincludedcontactprecautions,handhygiene, cohortisolation,aseptictechniqueforinsertionandmaintenance of indwelling devices,and enhanced environmental and equip-mentcleaning.Earlyidentificationoftheoutbreakandimmediate implementationofstrictcontactprecautionshelpedtocontainthe outbreak,togetherwithimprovedstaffingallocationintheNICU.
Table2 liststhelessons learnedin investigationand control duringthe8yearsofexperiencemanagingoutbreaksinanNNUin amiddle-incomecountry.
TwentypublishedoutbreakreportsfromAfricanNNUsoverthe last two decades were identified, withthe majority from Sub-SaharanAfrica(n=16),includingSouthAfrica(n=12)(Table3).15– 33 Very few of these published reports included an outbreak definition,butthosethatdidusuallycitedanoutbreakasasingle pathogen affecting two or more patients witha temporal and spatiallink(between7and10days,occurringonthesamewardor unit).One-thirdofreportsdescribedoutbreaksrestrictedtoNICU settings.Outbreakpathogenswerepredominantlybacterial,with highratesofantimicrobialresistance.ESBL-producingK. pneumo-niaewasthemostcommonoutbreakisolate(n=10),followedby multidrug-resistantA.baumannii(n=3).Twentypercentof out-breaks (4/20) were associated withthe introduction of a viral pathogenintotheNNUfromthecommunity,includingrotavirus, norovirus, RSV, and influenzavirus. The 20 outbreaks affected 524babiesresultingin177deaths(34%casefatalityrate),although threestudiesdidnotreportthenumberofneonataldeaths.The outbreaksourcewasidentifiedin50%ofcases:infusates(glucose, intravenousfluids,parenteralnutrition)(n=5),healthcareworker hands (n=4), the environment (mattresses, radiant warmers, suction catheters and bottles, milk buckets) (n=2), vectors (cockroaches) (n=1), and other patients (RSV) (n=1); some outbreaksinvolvedmultiplesourcesofinfection.Althoughsome publications did not report on the methods used to achieve outbreak control,commonly used measuresincludedenhanced hand hygiene, environmental cleaning, ward closure, cohort isolation,andtheintroductionofaseptichandlingofintravenous infusions.
Discussion
Given the reported frequency of NNU outbreaks in high-resourcesettings,itcanbeconcludedthatNNUoutbreaksinAfrica arelikelygrosslyunder-identifiedandunder-reported,evenatthe present studyinstitution. Using theexpectedannualrate of 10 outbreaksperNNU,1atleast80outbreaksatTygerbergHospital should have been identified for the study period. It is likely, therefore,thateveninthisrelativelywell-resourcedsetting(with access to laboratory investigations, IP and ID services), NNU outbreaksaremissedorundocumented.
In the two outbreaks in which strain-typing was utilized (S. marcescens (2012) and VRE (2013)), the use of expanded laboratory testing was instrumental in linking additional cases retrospectivelyandidentifyingtheoutbreaksource.This institu-tion’shighHA-BSIrate(particularlyfor‘endemic’K.pneumoniae BSI)suggestsongoingbacterialtransmissionwithsmallinfection clusters where epidemiological relatedness is not immediately apparent(intheabsenceofmoleculartyping).Infurthersupportof thishypothesisisthefactthatnotasingleK.pneumoniaeoutbreak
hasbeen documented since 1996, despitethis being the most frequentNNUHA-BSIpathogen,i.e.,implyingthat‘endemic’BSI pathogenslikeKlebsiella mayactually representpropagationof severallinkedinfectionclusters/outbreaks.
AnotherimportantdifferencefromtheTygerbergNNU experi-enceistheabsenceofS.marcescensintheAfricanNNUoutbreak literature. There is growing evidence of S. marcescens as an importantneonatalpathogenglobally,withsubstantialassociated mortality4 and long-term neurodevelopmentalmorbidity docu-mentedamongpatientsatthestudyinstitution.34Gram-positive organisms (VRE and MRSA) are also notably absent from the African NNU outbreak literature,whereas they were relatively
common outbreak pathogens at Tygerberg, albeit with low
mortality. Furthermore,all reports of viral pathogenoutbreaks came from South Africa, possibly reflecting easier access to virology laboratory services. Although there was no obvious influenceofseasonalityforbacterialoutbreaks,thevirusescausing outbreaks(rotavirusandinfluenzavirus)occurredduringtheusual southernhemispherepeaktransmissionseasonsforeach patho-gen.
Outbreak-associatedmortalityatTygerbergwassubstantially lowerthanthemortalityattheotherAfricanNNUs(7%vs.34%),
and even lower than mortality reported from high-income
countriesina recentsystematicreview (9%).Theavailabilityof NICUfacilities,anexcellentlaboratory,andIPservice,aswellas accesstobroad-spectrumantibiotics(particularlycarbapenems), wereprobablyimportantfactorsincontainingoutbreaksizeand limitingmortalityatthestudyinstitution.
Inthe20AfricanNNUoutbreakreportsincludedinthisreview, many supplied very limited information on the IP measures implemented. Future outbreak reports should include detailed descriptionsofinterventionsutilized,toexpandtheknowledgeof controlstrategies andtheirsuccessin low-resource settings.In addition, increased reporting of African NNU outbreaks will provide clearer estimates of the continent’s outbreak burden andpathogenspectrum.Additionaldataontheepidemiologyof HA-BSIinAfricanNNUsisalsourgentlyrequiredtoinformempiric
antibioticneonatalregimens.Strengtheningoflaboratoryservices andtheabilitytoconductHAIsurveillanceinAfricawillsupport both a better understanding of epidemiology and ability to investigate/report outbreaks. In particular, increased access to molecular typing services in African laboratories would be particularly helpful to integrate epidemiological and clonality dataduringtheinvestigationandcontrolofneonataloutbreaks.
The value of detailed outbreak investigation, institutional preparedness, and support of clinician leaders and hospital management in enforcing IP measures, cannot be overstated. OutbreaksontheNNUandespeciallyintheNICU,alwayspresenta crisisbecausethey affectbedavailability. Inmost low-resource settings,wardclosureduringoutbreaksisseldomimplemented,as diversionofneonataladmissionsisoftennotpossible.Giventhis reality,cohortnursingand‘isolation’inincubators(asaphysical barrier) are practical measures for outbreak management in AfricanNNUs.DealingwithanNNUoutbreakisacomplexprocess withmultifactorialchallengestoaddress,inadditiontostandard measures of case, contact, and source identification and the implementation of transmission-basedprecautions. These chal-lengesincludethehighnumberof‘contacts’asaresultofconstant
movement of babies across the NNU platform; pressure to
continueservicedeliverywhilecontainingtheoutbreak;insuf fi-cient isolation space; staff shortages preventing the dedicated allocationofstafftonurseinfected/colonizedbabies;insufficient equipment to allow for dedicated use; difficulty in ensuring adequate disinfection of shared items; and staff fatigue with protocolsandpersonalprotectiveequipment(PPE) recommenda-tions. Notwithstandingthesechallenges,in theauthors’ experi-encemostoutbreakshavebeenterminatedbya combinationof increased hand hygiene compliance rates, strict adherence to precautions, cohortisolation, enhancedenvironmental cleaning, andstaffeducation.
Inconclusion, outbreaksinhospitalizedAfricanneonatesare frequentbutunder-reported,withhighmortalityanda predomi-nance of Gram-negative bacteria. Breaches in IP practice are commonlyimplicatedandtheoutbreaksourceisconfirmedinless
Table2
Bestpracticesinneonataloutbreakinvestigationforlow-andmiddle-incomecountries.
1.Identifyanoutbreakorpotentialoutbreakasearlyaspossible(earlyidentificationismadepossiblebymeansofroutinesurveillance)andalertIPCstaff,clinicians,and microbiologistswhocommunicatewitheachotheronacontinualbasis.
2.Takepromptactiontoidentifyallcasesandcontacts.Createacasedefinitiontoidentifycasesandamendthedefinitionastheinvestigationintotheoutbreak progresses.Clearlydefinewhocanberegardedascontactsandbasethisdecisiononahigh(substantial)riskofexposuretothecase(s).Keeptrackofallthecontacts fromasearlyaspossible.Writedownalltherelevantdetails.Thisiscumbersomebutmostoftencomesinhandylaterwhencontactsbecomeinfected. 3.Implementappropriateisolationmeasuresimmediately.Thisincludeslimitedmovementofcasesandcontactsandclosureofaffectedroomsfornewadmissions.
Elevated(stricterandmoreextensive)isolationprecautionsoverandaboveprecautionsthatareusuallyputinplaceforasingleisolationcaseareoftenrequiredandare usuallyeffectiveinoutbreakcontrol.Cohortcasesandcontacts.Ensurethattheappropriatepersonalprotectiveequipment(PPE)andothersuppliesareavailable.Keep theminimumofsuppliesinsideisolationrooms;e.g.oneboxofglovespercribonly.
4.Reviewisolationmeasuresonadailybasiswiththestaffonduty.Includethenightshiftstaffaswellasthehousekeepingandadministrativestaff.Givefeedbackabout progressbeingmadewiththeoutbreakandemphasizetheneedforcontinuedisolationprecautionstokeepstaffmotivated.Alsoexplaintheisolationmeasuresto parents/caregiversandmakesuretheyunderstandwhatisexpectedofthem.
5.Draftaprotocoltogiveguidanceforthemanagementoftheoutbreak.Theprotocolsmustbeshort(onepage),easytoread,andmustcontainspecificactionstobe taken.Laminatethesepostersanddisplaythemintheisolationroomswheretheyarevisible.
6.Plotcasesandtheirlocation,movement,andotherrelevantdatasuchasdatesofpositiveisolatesonatimelineorGanttchart.Thiswillhelptoidentifytheindexcase, possiblesourceoftheoutbreak,andtheclinicalareasinvolvedintheoutbreak.
7.Calculatetheincidencerateandplotthenumberofnewcasesonahistogramsothattheprogressoftheoutbreakcanbemonitored.
8.Haveregular(dailyifneeded)meetingswithhospitalmanagement,infectioncontrol,microbiology,infectiousdiseases,clinicians,andnursingmanagerstogive feedbackabouttheprogressoftheoutbreak,isolationmeasures,thesituationintheaffectedareas,andplanstocontinueclinicalcareofneonatesnotpartofthe outbreak.Alsokeepneighbouringhospitalsinformed.Communicationisakeymeasure.
9.Ensurethatisolationprecautionsaremaintainedwhencasesorcontactshavetogoforsurgeryorwhencasesandcontactsaretransferredtootherhealthcarefacilities. 10.Monitorpeopleenteringtheisolationrooms(e.g.,consultantsandalliedhealthprofessionalssuchasdieticiansandradiographers),sincetheymaynotbeawareofthe
outbreak.Makesurethattheyareinformedandadheretotheisolationprecautions.
11.Makesurethatnon-compliancewiththeisolationprotocolisaddressedassoonaspossibleandthatthereasonforthenon-complianceisinvestigated. 12.Screenstaffonlyasalastresortandwhentheoutbreakinvestigationsuggeststhatthesourceoftheoutbreakmaybeduetostaffcarriage.
13.ScreenneonatestodeterminecarrierstatuswhendealingwithoutbreaksofVREandcarbapenem-resistantEnterobacteriaceae. 14.Doenvironmentalsamplingonlywhentheoutbreakinvestigationsuggeststhelikelihoodofenvironmentalsourcesoftheoutbreak. 15.Useachecklistforterminalcleaningoftheisolationroomsandensurethattheterminalcleaningoftheroomsissupervised. IPC,infectionpreventionandcontrol;VRE,vancomycin-resistantEnterococcus.
than50%ofcases.Programmestoimproveoutbreaksurveillance/ reportingandaddresslapsesinIPinAfricanNNUsareurgently required.
Funding None.
Conflictofinterest
Noconflictofinteresttodeclare. References
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Table3
PublishedoutbreaksaffectinghospitalizedAfricanneonates(January1,1996toJanuary1,2016). Firstauthor Outbreak
year/s
Country Setting Pathogen Casesa
(n)
Deaths (n)
Presumedorconfirmed outbreaksource
IPmeasuresforoutbreakcontrol Ben-Hamouda15
1996 Tunisia Ward Klebsiellapneumoniae ESBL
40 NR Wardenvironment NR
Newman16
1996 Ghana NICU SalmonellagroupG 6 0 Mattresses/radiantwarmer WC Cotton17
1996 S.Africa Ward Klebsiellapneumoniae ESBL
32 15 Cockroachesinvinylwall covering
WC,HH,removalofvinylwall coverings,fumigation,patient screening
Pillay18
1996 S.Africa Ward Klebsiellapneumoniae ESBL
33 13 Unknown WC,HH,patientisolation,
enhancedenvironmental cleaning
Pillay19
1997 S.Africa NICU Acinetobacter baumannii(MDR)
9 2 Suctioncathetersandbottles WC,HH,single-usecatheters forsuctioning
vanNierop20
1998 S.Africa NICU Enterobactercloacae 12 9 Intravenousinfusions,handsof staff
HH,discardedallintravenous solutions
Gregersen21
1998 S.Africa NICU Klebsiellapneumoniae ESBL
6 2 Unknown HH
Jeena22
1999 S.Africa NICU Acinetobacter baumannii(MDR) 5 NR Presumedenvironmental source WC,HH,cohortisolation, patientscreening Moore23
2001 Egypt NICU Predominantly
Klebsiellapneumoniae ESBL 88(R), 24(P) 59(R) Intravenousglucose preparations
Reviewedasepticpreparation ofintravenousfluids,HH Bouallègue-Godet24
2002 Tunisia NNunit Salmonellaenterica serotypeLivingstone ESBL
16 2 Notidentified,possible environmental
HH,patientisolation,enhanced environmentalcleaning Boukadida25
2002 Tunisia NICU Klebsiellapneumoniae ESBL
14 14 Contaminationofintravenous infusions,poorhandhygiene
NR
Marais26 2002/3
2004
S.Africa NNunit Klebsiellapneumoniae ESBL
17 10
9 6
Intravenoussupplements Asepticpreparationof intravenousfluids,HH,general IPmeasures
Moodley27
2005 S.Africa Ward Klebsiellapneumoniae ESBL
26 22 Intravenousglucose preparations
HH,stoppeduseofmulti-dose vials
Visser28
2006 S.Africa Kangaroo Careward
RSV 23 2 RSVidenticalstrainidentified
fromchildonpaediatricward NR Eibach29 2007–2012 Ghana Ward Klebsiellapneumoniae
ESBL(4clusters)
20 NR NR NR
Holgate14
2009 S.Africa NNunit H1N1influenza 5 1 Infectedstaffandpatients Cohortisolation deVilliers30
2010 S.Africa NNunit Rotavirus 44 9 Proportionof community-acquiredvs.nosocomial diseaseNR
NR
Mshana31 2010 Tanzania Ward Enterobactercloacae
ESBL
17 6 Contaminatedmilkbucket HH,enhancedenvironmental cleaning
Mshana32
2010 Tanzania NNunit Klebsiellapneumoniae ESBL(3clusters)
28 26 6
Possiblecommonsource, colonizedstaff
NR
ProMedMail33
2010 S.Africa Ward Norovirus 17 6 Suspectedinfectedmotheror
staffmember
NR
ESBL,extended-spectrumb-lactamaseproducer;HH,handhygiene;IP,infectionprevention;MDR,multidrug-resistant;NICU,neonatalintensivecareunit;NNunit,neonatal unitadmittinginbornandoutbornbabies<4weeksofage;NR,notreported;P,prospective;R,retrospective;RSV,respiratorysyncytialvirus;S.Africa,SouthAfrica;WC,ward closure.
a
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