Antimicrobial storage and antibiotic knowledge in the community: a cross-sectional pilot study in north-western Angola

Antimicrobial

storage

and

antibiotic

knowledge

in

the

community:

a

cross-sectional

pilot

study

in

north-western

Angola

Joana

Cortez

*,

Edite

Rosário

,

João

E.

Pires

,

João

Taborda

Lopes

,

Moisés

Francisco

,

Erika

Vlieghe

,

Miguel

Brito

a_{HealthResearchCentreofAngola,CISA,Caxito,Angola} b

WHORegionalOfficeforEurope,Copenhagen,Denmark

c

NationalInstituteofPublicHealth,MinistryofHealth,Luanda,Angola

d

DepartmentofClinicalSciencesAntwerp,InstituteofTropicalMedicine,Antwerp,Belgium

e

UniversityHospitalAntwerp,Antwerp,Belgium

f

UniversityofAntwerp,Belgium

g_{LisbonSchoolofHealthTechnology,PolytechnicInstituteofLisbon,Lisbon,Portugal}

ARTICLE INFO Articlehistory: Received12March2017

Receivedinrevisedform10May2017 Accepted11May2017

CorrespondingEditor:EskildPetersen, Aar-hus,Denmark Keywords: Antimicrobialstorage Antibioticknowledge Community Angola SUMMARY

Background:Antimicrobialsaredrugsthatwereoncelifesaversandmainlycurative.Nowadaystheir valueisincreasinglyunderpressurebecauseoftherapidandworldwideemergenceofantimicrobial resistance,which,inlow-resourcesettings,frequentlyoccursinmicroorganismsthatarelikelytobe transmittedinthecommunity.

Methods:Thiswasacross-sectionalpilotstudyincluding102householdswithinthe10thHealthand DemographicSurveillanceSystemroundinDande,BengoProvince,Angola.

Results:Ofthetotal102householdspiloted,79(77.45%)wereurban.Fifty-sevenrespondentswerefemale (56.44%),andthemeanageoftherespondentswas39.7015.35years.Overall,storageofantimicrobials wasfoundin55/102households(53.92%).Morethan66%oftheantimicrobialsstoredwereprescribedby ahealthprofessionalandthemajorityofantimicrobialswereboughtatpharmaciesoratastreetmarket. Penicillin and itsderivatives,antimalarial drugs,and metronidazolewere theantimicrobials most frequently stored. Householdswith femalerespondentsreported storingany drugsat home more frequently (82.50%;p=0.002)andalsostoringantimicrobialsmorefrequently(64.91%; p=0.016)as comparedtohouseholdswithmalerespondents.Reporteduseofantimicrobialswassignificantlyhigher inurbanhouseholds(60.76%,48/79)ascomparedtoruralhouseholds(30.43%,7/23)(p=0.010).Overall, 74of101respondents(73.26%)reportedhavingalreadyheardaboutantibiotics.Thecommonreasons givenfortheirusewerecoughandotherrespiratorysymptoms,wounds,fluandbodymusclepain,fever, bladdercomplaints,anddiarrhoeaand/orpresumedtyphoidfever.Nearly40%(28/74)oftherespondents thoughtthatantibioticsshouldbestoppedassoonasthepersondoesnotfeelsickanymore. Conclusions:Communityinterventionsforappropriateuseofantibioticsshouldbedesignedwitha specialfocusonwomen.Thisshouldbedonethroughpublicawarenesscampaignsandimprovingaccess toreliablemedicalservices.Drugprescribersarekeynotonlytoappropriateantimicrobialprescription, but also to adequate dispensing, and are strong advocates for the possible misconceptions on antimicrobialusagebylaypeople.

©2017TheAuthor(s).PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases. ThisisanopenaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Antimicrobials are drugs that were once lifesavers, mainly curativeformeningitis,pneumonia,andotherinvasiveinfections, aswellasenablingsaferchildbirth, surgicalprocedures,and,in

high-resource countries, organ transplantation and oncological treatmentregimens(Marstonetal.,2016).Nowadaystheirvalueis increasinglyunderpressurebecauseoftherapidandworldwide emergenceofantimicrobialresistance(AMR).

In low-income countries, AMR frequently occurs in micro-organismsthatarelikelytobetransmittedinthecommunity,such asthepathogenscausingpneumonia,diarrhealdiseases, tubercu-losis, sexuallytransmitted diseases, and malaria (World Health

* Correspondingauthor.

http://dx.doi.org/10.1016/j.ijid.2017.05.011

1201-9712/©2017TheAuthor(s).PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

ContentslistsavailableatScienceDirect

International

Journal

of

Infectious

Diseases

Organization, 2017a). This complex health problem is likely associated withvarious factors,in particular the excessive and inappropriateuseofantimicrobials(LaxminarayanandHeymann, 2012).Any antimicrobial use, whether or not appropriate, will causeselectivepressure,whichmayleadtotheselectionofmore resistantpathogens.

A study based on sales data from retail and hospital pharmacies in national sample surveys estimated that the worldwide consumption of antibiotics in healthcare settings overthefirstdecadeofthenewmillenniumincreasedbymore thanonethird(VanBoeckeletal.,2014).Inthatstudy,thelackof dataforSub-SaharanAfricawasparticularlystriking.Worldwide, thelargemajorityofantimicrobialuseoccursinthecommunity, where such drugs can readily be obtained, even without a prescription(Ngadoetal.,2014;Landersetal.,2010;Hoaetal., 2009). Unfortunately in-depth information on antibiotic con-sumptioninthecommunitiesworldwideisveryscarce,especially inlow-resourcesettings.

Ithasbeenshownthatstoringantimicrobialsathomeisrelated totheirinappropriateuse(Yuetal.,2014;Togoobaataretal.,2010). It is also known that resource-poor healthcare systems in the developingworldtendtouseantimicrobialsinappropriatelymore often(Kardasetal.,2005).Angoladoesnothavenationalantibiotic treatmentguidelinesandhasalaxregulatorysystem,similarto otherdeveloping countries(Laxminarayanand Heymann,2012; Morganetal.,2011;Hollowayetal.,2016).

The purpose of this pilot study was to describe the first prevalenceestimatesforantimicrobialstorageinthecommunity, explore factors associated with storage, and to assess basic knowledgeonantimicrobialsamongthegeneralpublicinBengo ProvinceinthenorthofAngola.Additionally,thisstudyservedasa fieldtestfortheadequacyofthedatacollectiontoolandplanning ofhumanresourcesandlogisticsinpreparationforalargerstudy. Methods

Studyareaandsite

The study was conducted in Bengo Province, about 60km northwestof Luanda,andcoveredatotal areaofapproximately 4763.6km2inanareawheretheHealthResearchCentreofAngola (CISA)hasruntheDandeHealthandDemographicSurveillance System(HDSS)since2009.TheDandeHDSSinitialcensuscovered approximately60000residentslivinginmorethan15600 house-holds(Sousa-Figueiredoetal.,2012),spreadover70hamlets,60% ofthemlocatedinruralareas.TheHDSSaimstoproviderelevant health, demographic, and socioeconomic data to inform local policiesandresearchonendemicdiseases(Fançonyetal.,2012; Piresetal.,2013;Magalhãesetal.,2012).Agricultureisthemain economicactivity, attractingsome migrantworkersfromother parts of the country. Fishing in lakes and rivers and charcoal exploitationarealsoimportanteconomicactivities.Theexisting industrialactivityislinkedtostoneandsand extraction,which suppliestheconstructionbusiness.Theareaisholoendemicfor Plasmodiumfalciparummalaria,andtheprevalenceofHIVamong adults aged 15–49 years nationwide was about 2.2% in 2015 (UNAIDS, 2017), withhigherprevalencerates inprovinces with internationalborders.

Studydesignandpopulation

Trained field workers visited a convenience sample of 102households supervised bythe principalinvestigator. Urban hamlets were classified according to the National Statistical InstituteofAngolaasagglomerationsof2000ormoreinhabitants andabasicinfrastructure(MinistériodoPlaneamento,2011).

Studyvisitswereperformedaftera2-daytrainingprogramme onthetheoreticalbackgroundofantimicrobialsandconceptsof resistance, including role-play exercises adapted to the field workers’knowledgeaboutantimicrobials.Theterm‘antimicrobial’ was used forany anti-infectivedrug (i.e.,antibiotics,antivirals, antifungals,anthelmintics,andtuberculostaticdrugs).‘Antibiotic’ wasthetermusedtotesttheparticipants’knowledgeonthistopic. A standardized questionnaire with questions on knowledge of antibioticsandresistancewasfilledoutduringtheinterview,and therespondentswererequestedtobringanymedicationstoredat homewiththem.Verbalinformedconsentwasobtainedbeforethe questionnaire was completed.The respondent was any person livinginthehouseholdatthat time,whowas aged16years or above. The trained field worker collected the name of any medication (drugs themselves and/or prescriptions) and asked whetherthatdrughadbeenprescribed,whethertheposologyhad beenexplained,andwhereithadbeenbought.Amagnifyinglens wasusedtohelpfieldworkerstoretrievetheinformationfrom damagedblisterstripsorprescriptions.

These102householdswereusedasapilotstudyforanongoing cross-sectionalstudythroughthe10thHDSSround,whichstarted inJuly2016andwhichwascompletedattheendofJanuary2017. Statisticalanalysis

Data were analyzed using Stata 14.0 software (StataCorp, CollegeStation,TX,USA).Frequenciesandproportionswereused to describe the study population in relation to the relevant variables.Oddsratios,95%confidenceintervals,andp-valueswere computed to assess the presence and degree of association betweenantimicrobialstorageanddemographiccharacteristics.

The Chi-square test was used tocompare proportions(sex, distancetonearesthealthfacility,placeofresidence(rural/urban), andliteracy)withtheconsumptionofantimicrobials,andap-value of<0.05wasconsideredstatisticallysignificant.

Denominatorsvaryintheanalysisbecausenotallrespondents answeredeveryquestioninthesurvey.

Results

Socio-demographiccharacteristics

Ofthetotal102householdspiloted,79(77.45%)wereurbanand 23 (22.55%) were rural. Fifty-seven respondents were female (56.44%). The mean age of the respondents was 39.7015.35 years;72/99(72.73%)wereabletoread.Amongtherespondents who couldprovideinformation on monthlyhouseholdincome, nearly32%(61/102)declaredhavinglessthan10000AOAorno monthlyhouseholdincome(100AOA=0.55EUR/0.60USD). Storageofantimicrobials

Seventy-two of the 102 households (70.59%) stored any medication at home, and 55 of the 102 households (53.92%) storedantimicrobials.Morethan66%oftheantimicrobialsstored wereprescribedbyahealth professional.Morethan 60%ofthe respondents(62/102)hadboughttheantimicrobialsatapharmacy and15.68%(16/102)hadboughtthematastreetmarket.

Penicillinanditsderivates,antimalarialdrugsand metronida-zolearethemostfrequentlyantimicrobialsstoredrespectively,29/ 102(28.43%)and24/102(23.53%),forantimalarialand metroni-dazole. Quinolones were reportedly taken in 12.75% of the households (13/102), and chloramphenicol and trimethoprim– sulfamethoxazolein10.78%(11/102)each.

Households with female respondents reported storing any drugs at home more frequently (82.50%) (p=0.002) and also

storingantimicrobialsmore frequently(64.91%)ascompared to householdswithmalerespondents(Table1).

Reporteduseofantimicrobialswassignificantlyhigherinurban (60.76%,48/79)ascompared toruralhouseholds (30.43%,7/23) (Table 1). Those who lived near a healthcare facility (i.e., the nearesthealthfacilitywithin10kmdistance)storedantimicrobials moreoften(48/79,60.76%)thanthosewhohadtotravelalong distancetotheirhealthfacilities(7/23,30.43%)(Table1).

Respondentswhowereabletoreadstoredmoreantimalarial drugsathome(22/72,30.56%)ascomparedtothosewhocouldnot read (2/27, 7.41%) (Chi-square=5.73, p=0.017). This association was not statistically significant to the overall storage of anti-microbials(Table1).

Knowledgeonantimicrobialusageandresistance

Overall,74of101(73.26%)respondentsreportedhavingalready heardaboutantibiotics.Thecommonreasonsgivenfortheuseof antibioticswerecough and otherrespiratorysymptoms (28/74, 37.84%),wounds(22/74,29.73%),fluandbodymusclepain(23/74, 31.08%),fever(14/74,18.92%),bladdercomplaints(13/74,17.57%), and diarrhoea and/or presumed typhoid fever (10/74, 13.51%). Nearly 40% (28/74) of therespondents thoughtthat antibiotics should be stopped as soon as the person does not feel sick anymore, and 42/74 (56.76%) thought they should only stop accordingtotheprescription.Only13/74(17.57%)respondentshad alreadyheardaboutantimicrobialresistance, andnearlyhalfof them(6/13)thoughtthatit isthepersontakingthedrugswho becomesresistanttotheireffects,notthemicrobes.

Discussion

Thisappearstobethefirststudyonantimicrobialstoragein Angolaandoneofonlyafewstudiesonantimicrobialstoragein communities in low-resource settings. The overall storage of antimicrobialsinthispopulationwasfoundtobehigh.Although the questionnaire did not specifically address whether the antimicrobials were used on a second occasion, this is highly probable, as shown previously in other studies performed in similarsettings(WorldHealthOrganization,2015;Lvetal.,2014; Biswasetal.,2014a;Ocanetal.,2015;Dingetal.,2015).

There are some limitations to the study findings. First, convenience sampling was applied, thus there is an important riskof selectionbias,as mostofthehouseholds includedwere locatedinurbanareasinthevicinityofCISA,forlogisticalreasons. In addition, thequestionnairewas appliedduring themorning hourswhenwomenaremorefrequentlyfoundathome,andthus

womenweremorelikelytobethehouseholdrespondent.When asked for stored medication, women were also more likely to retrieveanystoredmedication,astheyaremuchmoreinvolvedin housekeeping activities. This might indicate that there are limitations in studyingantimicrobial storageat home for male respondentsandthatadifferentstudymethodologyisneededto assessthestorageofantimicrobialsbymales.Nevertheless,female respondentsandurbanhouseholdswereidentifiedasthosemore oftenstoringantimicrobialsathome.

In contrast to a study performed in Bahir-Dar, Ethiopia (Gebeyehuetal.,2015), inthepresentstudy, urbanhouseholds stored more antibiotics than rural households. This might be related to the fact that this HDSS covers a wider and more dispersed area, which leads to challenges in the exchange of informationandbasicknowledgeonthecorrectuseof antimicro-bials, as wellas the probable easier access topharmacies and hospitalsfor urbanhouseholds.This‘urban’storageisprobably verymuchalignedwiththehealth-seekingbehaviourshowninthe presentstudydata,inwhich morethan60%of therespondents bought antibiotics with a prescription and at pharmacies or hospitals.

Theeffectivenessofantibioticsisthreatenedbythe antimicro-bialresistancethatcanarisefrominappropriateself-medication andincompletetreatmentcourses(Hoaetal.,2009).Inthispilot study, nearly 40% of the respondents thought that treatment shouldbestoppedonce thesymptomshavesubsided.Thisisa higherpercentagethanreportedinsimilarstudiesinChina(Wun etal.,2013)andMalaysia(Fatokun,2014).Studieshaveshownthat this discontinuation might bedue toa lack of knowledge and awareness regarding antibiotic use, the nature of the health problems,andtheextentofhealthprofessionaladvice(Fatokun, 2014;Grossoetal.,2012;Pechereetal.,2007).

Mostofthestoredantimicrobialswerepenicillinand deriva-tives,metronidazole,andantimalarials.Penicillinconsumptionis frequentlymentioned inothersimilarstudies,includingstudies fromEthiopia(Gebeyehuetal.,2015;Desalegn,2013;Fentaetal., 2013;Getachewetal.,2013),Uganda(Ocanetal.,2014),Indonesia (Widayatietal.,2011),andGuatemala(Ramayetal.,2015).

Coughandotherrespiratorysymptoms(37.84%),fluandbody musclepain(31.08%),wounds(29.73%),andfever(18.92%)were thediseasesymptoms/conditionsforwhichantibioticsweremore commonlyreportedtobeused.Respiratorytractinfectionwasalso foundtobethemaindrivingforceforantibioticusageinEthiopia (Gebeyehu et al.,2015), Bangladesh (Biswas et al., 2014b), and otherAsiancountries(Okumuraetal.,2002;Bietal.,2000).

A striking finding was that more than a quarter of the households interviewed reported the usage of antibiotics to combat flu and body musclepain, signs and symptomstypical of viral diseases. This reinforces the lack of knowledge and awarenessofantimicrobialuseandtheoriginofhealthproblems. Interestingly,thosehouseholds inwhich therespondentwas more literatestoredmore antimalarials.Althoughotherstudies have found that a lower educational status is associated with inappropriate overalluse of antibiotics (Gebeyehu et al., 2015; Awadetal.,2005;Sapkotaetal.,2010;Chowdhuryetal.,2009; Osemene andLamikanra, 2012),a statisticallysignificant differ-enceinoverallstorageofantimicrobialsaccordingtothelevelof literacywasnotfoundinthepresentstudy.

Themisunderstandingoftheparticipantsaboutantimicrobial resistance is based on their perception that resistance is an attributeofpeopleandnotofmicrobes.Researchpublishedbythe World Health Organization (WHO) in 2015showed that three-quartersofpeopleinpoorandmiddle-incomecountries misun-derstoodtheproblemthatway(WorldHealthOrganization,2015). This study was planned as a pilot test. By the time a full assessmentHDSSroundiscomplete,itisexpectedthataclearer

Table1

FactorsassociatedwiththestorageofantimicrobialsinBengoProvince,Angola. Associatedfactors %storage p-Value

Sex 0.016 Female 64.9 Male 40.9 Age,years 0.22 30 66.7 30–50 51.3 >50 45.5 Placeofresidence 0.01 Urban 60.8 Rural 30.4

Distancefromhealthcarefacility 0.01

10km 60.8

>10km 30.4

Literacy 0.17

Yes 59.7

pictureofoverallantimicrobialstorageinthiscommunitywillbe obtained,andassociationswithcertainfactorssuchashousehold income,numberoffamilymembersperhousehold,literacy,and age will be performed. It is also intended to determine any associations between knowledge on antimicrobials and their storage.Thecurrentstudyispartofalargerprojectthataimsto assessandimproveknowledge,attitudes,andpracticestowards antimicrobial use, using sales data from pharmacies, hospital-basedpointprevalence studies,in-depthinterviewsat markets, andfocusgroupdiscussionswithdoctors,nurses,andteachers, leadingtoabroaderassessmentofthispublichealthproblem.

As a cross-sectional study, it was not possible to check for temporalorgeographicaltrends.Therecallperiod,whichwasplaced withinthecontextoftherecentyellowfeveroutbreakandhigh all-causemortalityinAngola(WorldHealthOrganization,2017b),as well as the methodology used, probably allowed for a higher percentageofantimicrobialstoragethanWHOreportsforsimilar settings.Nevertheless,itisbelievedthatthisfiguremaybereliableas a benchmark forantimicrobial storage in low-resource settings. Additionally,storage ofantimicrobialsathome mayend in self-medicationatanytime.Accesstohealthservices,inparticularthe feelingofsatisfaction/dissatisfaction,wasnotassessed.Thisvariable hasbeenshownasoneofthepredictorsofinappropriateantibiotic use(Gebeyehuetal.,2015;Fernandesetal.,2014;Spellberg,2014). Beforethis pilotstudy,a theoretical background was given to thefield workers,routinemeetingswereheldwiththefieldworkersduring theHDSSround,astructuredquestionnairewasdeveloped,anda magnifying lenswas provided to improveinformationgatheredfrom damaged blisters. Nevertheless, the use of medical jargon was inevitable,whichmighthavemadeitdifficulttoretrievethecorrect namesforthesemedications.

Inspiteoftheselimitations,itisbelievedthatthispilotstudy followedbytheongoingstudyofthe10thDandeHDSSroundwill provideinformation ofuniquesignificanceregardingthe preva-lence of antimicrobial storage in Angolan communities, which couldboostresearchininter-relatedareas.Itcouldalsohelpthe drugregulatoryauthoritiesinAngolatoimplementrestrictionsfor thesupplyanddemandchainofthesedrugs,aswellasbehelpful inthedesignandsettingupoftargetededucationcampaigns.

In conclusion, this pilotstudyrevealed a highproportion of antimicrobialstorageinhouseholdsinDande,BengoProvince,in particular in urban households and households where women wereresponsible.A highdiscontinuation rate of the treatment coursewasalsofound,aswellasahighproportionofprescription and pharmacy-driven health-seeking behaviour and an almost unacknowledgedconceptofantimicrobialresistance.Theongoing 10thHDSSroundstudywillhopefullygiveaclearerpictureofthe situation.

Communityinterventionsfortheappropriateuseofantibiotics shouldbedesignedwithaspecialfocusonwomen,throughpublic awarenesscampaigns and improving accesstoreliable medical services. Drug prescribers are key not only to appropriate antimicrobialprescription, butalsotoadequatedispensing,and arestrongadvocatesforthepossiblemisconceptionson antimi-crobialusagebylaypeople.

Conflictofinterest

Theauthorsdeclarethattheyhavenocompetinginterests. Acknowledgements

The authors wish to acknowledge all CISA staff for their continuoussupportduring thefieldwork,and very importantly thankalltheparticipantswhoagreedtotakepartinthestudy.This workwasfundedbythepromotersofCISA(Camões Institutoda

Cooperação e da Língua, I.P, Fundação Calouste Gulbenkian, GovernoProvincialdoBengoandMinistériodaSaúdedeAngola), which played no role in either the design of the study or in interpretingthefindings.

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