Pertussis may be the cause of prolonged cough in adolescents and adults in the interepidemic period

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braz j infectdis.2015;19(1):43–46

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

Original

article

Pertussis

may

be

the

cause

of

prolonged

cough

in

adolescents

and

adults

in

the

interepidemic

period

Analíria

Moraes

Pimentel

a,∗

_,

_Paulo

_Neves

_Baptista

a

_,

Ricardo

Arraes

de

Alencar

Ximenes

b

_,

_Laura

_Cunha

_Rodrigues

c

_,

_Vera

_Magalhães

b

_,

Pert

–

Pertussis

Study

Group,

Andrea

Rosane

Sousa

Silva

d

_,

_Nadjla

_Ferreira

_Souza

e

_,

Deize

Gomes

Cavalcanti

de

Matos

e

_,

_Ana

_Kelly

_Lins

_Pessoa

f

a_Pediatric_Infectious_Diseases_Service,_School_Hospital,_Universidade_de_Pernambuco,_Recife,_PE,_Brazil b_Tropical_Medicine_Department,_Universidade_Federal_de_Pernambuco,_Recife,_PE,_Brazil

c_Department_of_Infectious_and_Tropical_Diseases,_London_School_of_Hygiene_and_Tropical_Medicine,_University_of_London,_London,_UK d_Universidade_de_Pernambuco,_Recife,_PE,_Brazil

e_Laboratório_Central_de_Pernambuco,_Recife,_PE,_Brazil f_Laboratório_Marcelo_Magalhães,_Recife,_PE,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received19February2014

Accepted1September2014

Availableonline14October2014

Keywords:

Pertussis(whoopingcough)

Prolongedcough

Adolescentsandadults

Prevalence

a

b

s

t

r

a

c

t

Objective:Thisstudywasaimedtoevaluatetheprevalenceofpertussisinadolescentsand

adultswithcoughlastingmorethan14daysandlessthan30days.

Methods:Thisisaprospectiveobservationalstudyininterepidemicperiodofpertusis.Ten

publichealthoutpatientclinicsinthecityofRecife,Brazil,wererandomlyselectedforthe

study.Thestudypopulationconsistedofindividualsaged10yearsandoverwithcoughthat

hadlastedbetween14and30days.Nasopharyngealswabswerecollectedforcultureand

PCRinordertoidentifyBordetellapertussis.WeadoptedtheCentersforDiseaseControland

PreventionintheUS(CDC)deﬁnitionofcasesofpertussis.

Results:Atotalof192individualswereidentiﬁedassuspectedcases.Theirmeanagewas

40.7years.Pertussiswasconﬁrmedin10ofthe192suspectedcases,withanestimated

prevalenceof5.21%(95%conﬁdenceinterval2.03–8.38).Allcasesmettheclinicalcase

deﬁ-nitionforpertussis;onesuspecthadbothcultureandPCRpositive.PCRconﬁrmed100%of

thecases,7/10byPCRand3/10byepidemiologicallinkagewithacaseconﬁrmedbyPCR.

Conclusion: Duringaninterepidemicperiod,1in20casesofprolongedcoughhadpertussis,

suggestingthisisanimportantcauseofprolongedcoughinadolescentsandadults.

∗ _{Corresponding}_author_at:_Núcleo_de_{Pós-Graduac¸ão}_Rua_Arnóbio_Marques,_310,_Recife,_Pernambuco,_ZIP_Code:_50100-130,_Brazil.

E-mailaddress:analiriapimentel@terra.com.br(A.M.Pimentel).

http://dx.doi.org/10.1016/j.bjid.2014.09.001

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44 Introduction

Epidemicsofpertussis,anincreaseinofthenumberof

per-tussiscasesinadolescents,adultsandinfantsyoungerthan

sixmonthsofagehavebeenreportedinseveralregionsofthe

world.1–3 _Adolescents_and_adults_have_often_been_identiﬁed

asthe mainsourceofpertussis outbreaks amongst

house-holdmembers.4–6TheWorldHealthOrganizationestimates

that there were around 16 million cases of pertussis and

195,000deathsworldwide,95%ofwhichwereindeveloping

countries.2

Theclinicalpresentationofpertussisinadolescentsand

adultsisoftenatypical,withaprolonged,persistent,

nonspe-ciﬁccoughandintheseagegroupsthediagnosisofpertussisis

seldomconsidered.7–9_Although_many_studies_have_reported

thatprolongedcoughinadolescentsandadultsmaybe

per-tussis, theactual prevalenceofpertussis inthis agegroup

remains underestimated.2 _In _2010,_the _Centers _for _Disease

ControlandPreventionintheUS(CDC)registered27,550cases

ofpertussisintheUS,andinEuropetheEuropeanCenterfor

theControlandPreventionofDiseasesregistered15,749cases,

withahigherprevalenceinadolescentsbetweentheagesof

10and14years.10,11_In_studies_conducted_in_different_regions

oftheworldtheprevalenceofpertussisamongstadolescents

and adultswith prolonged cough has varied from 10% to

32%.9,12,13_The_variety_of_diagnostic_methods_and_case

deﬁni-tionsusedmaybeoneofthemajorreasonsforthedifferences

intheobservedprevalence.7,9,14,15_Nonetheless,_these_studies

havecontributedtostrategiesforcontrollingthesurveillance

ofpertussisinthesecountries.2,10,11

InBrazil,sincetheintroduction ofthe pertussisvaccine

in 1980, the number of reported cases fellsharply with a

sustaineddownwardtrend.Howeverin2011,583casesof

per-tussiswereconﬁrmed.Amongsttheconﬁrmedcases,76.3%

were infants under 1 year of age, the group with highest

incidenceand mortalityrates.16 _In_the _city _of_Recife,_most

notiﬁcationsofpertussisarehospitalizedcases.Astudy

car-riedoutinRecifeidentiﬁedthatadultsandadolescentsolder

than11.5yearswerethesourceofinfectionsfor70%of

per-tussiscases.4_However,_this_study_analyzed_cases_of_pertussis

inadultcontactsofchildrenwithpertussis.17

Thisstudyisaimedtoevaluatetheprevalenceofpertussis

inadolescentsandadultswithcoughlastingmorethan14

daysandlessthan30days.

Methods

This is a prospectiveobservational study in interepidemic

periodof pertussis.Thestudy was conductedin10 public

healthoutpatientclinicsinthecityofRecife,Brazil.The

out-patientclinicsfromwithinthecity’ssixHealthDistrictswere

randomlyselectedwithproportionalprobabilityofthe

num-berofpatientsattended.Healthprofessionalsandindividuals

attendingthehealthclinicswereinformedofthestudy.During

theperiodfromAugust2010toJuly2011,thoseovertheageof

10years,withcoughlastingmorethan14daysandlessthan

30 days were identiﬁed. Nasopharyngeal swabsfor culture

andPCRwerecollectedfromallparticipants.Individualswho

were immunocompromised, suffered from TB,had chronic

bronchitis,otherchronicdiseaseswithcough,orusingdrugs

that cause coughing wereexcluded from the study.A

sus-pectedcaseofpertussiswasconsideredasaconﬁrmedcaseif

theindividualpresentedacoughandapositive

nasopharyn-gealswabculture,ormettheclinicalcasedeﬁnitioncriteria

forpertussisandhad apositivePCR.Thecriteriafor

deﬁn-ingaclinicalcaseofpertussiswere:acoughformorethan

14days,associatedwithatleastoneothersymptom:

parox-ysmal cough, inspiratory whooping, post-tussive vomiting

regardless ofage and vaccination status. An

epidemiologi-callyconﬁrmedcasewasconsideredwhentheindividualmet

theclinicalcriteriaofapertussiscase,hadanegativeculture

and/orPCR,butwasincontactwithanindividualwith

per-tussisconﬁrmedbycultureorPCR.Materialfortheculture

and PCR wascollected bynasopharyngeal swabfrom

indi-vidualnostrilsforeachprocedure.Theswabsforcollecting

theculturewereinoculatedinatransportmediumof50%of

theRegan-Loweconcentrationmedium(OxoidLtd.,Columbia,

MD)forthecultureandforthelaboratoryinaReaganLowe

medium(Oxoid.Ltd.,Columbia,MD),madeselectivebythe

addition of40mg/Lcephalexin. The coloniessuspected as

being B.pertussiswere conﬁrmedbybiochemicaltests.The

real-time PCR used primers and TaqMan® _probes,

speciﬁ-cally for the IS 481 region.14,18,19 _The_study _was _approved

by the Ethics Committeeat Hospital Oswaldo Cruz,

regis-trationnumber 029/2008.All participantssignedtheTerms

ofFree,InformedConsent.Datawere codedandprocessed

using Epi-info 6.0.4 (CDC). The descriptive analysis of the

datawasconductedbyfrequencydistributionandthemeans

withtherespectivestandarddeviations.Inthecomparative

age analysisofthesuspected cases,accordingtopositivity

forpertussis,thestudentt-testwasappliedtoindependent

samplestestedfornormalitybytheKomogorov–Smirnovtest.

Intheanalysisofassociations,whentheindependent

vari-able was categorical, the Fisher’s exact test was applied.

The statistical signiﬁcance adopted for the study was 5%

(p<0.05). Aprevalenceof25%was assumedforcalculating

thesamplesize,anacceptablemaximumerrorof6%anda

conﬁdence intervalof95%.Theestimatedrequiredsample

was 201 patients. The study was conducted in 10

outpa-tientclinicsfromamongstthe12randomlyselectedclinics.

Twoclinicswereexcludedsinceitwasnotpossibletoselect

patientsduetooperationaldifﬁculties.Thepatients

identi-ﬁedattheexcludedclinicsweretransferredtootherclinics

inthe same district,whichmadepart oftheselected

clin-icsandcorrespondedto5.26%(10/192)oftheselectedsample

total.

Results

Atotalof192individualswereidentiﬁedagedover10years

andwithcoughlastingformorethan14days.Themeanage

was40.7years,rangingfrom 10to84yearsand aSD±17.8

years. Ofthese, 55.7% (107/192)were over 40 years of age,

27.6%(53/192)wereagedbetween20and39yearsand16.7%

(32/192)between10and19years.Atotalof70.0%(134/192)

ofthesuspectedcaseswerefemale;182/192ofthesuspected

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brazj infect dis.2015;19(1):43–46

45

Table1–Criteriaforconﬁrmingthediagnosisof pertussisinadolescentsandadultswithaprolonged cough.

Positiveforpertussis Positive (%) 95%CI

Criteriaforconﬁrmation

Culture 1/10 10% 0.25–44.5%

Real-timePCR 7/10 70% 34.7–93.3%

Epidemiologicallinkage 3/10 30% 6.7–65.2%

remaining10 individualswho reportedhavingreceivedthe

4-doseDPTvaccinewere agedbetween10and19years.Of

the10conﬁrmedpertussiscases,thevaccinationstatuswas

reportedbythreeindividuals,two conﬁrmedthattheyhad

receivedfour dosesofDPT,andoneconﬁrmedthreedoses.

Ofthese,onewasdiagnosedwithpertussis bycultureand

PCR,and the others, byPCR. Ofthe 192suspected

pertus-siscases, 171/192(89%) reportedcough ofbetween14 and

21 days and 21/192 (11%) for more than 21 days.

Inspira-torywhoopingwasreportedby120/192(62.5%),cyanosisby 27/192(14.1%)andpost-tussivevomitingby152/192(79.1%).

Amongstthe192suspected cases,pertussiswasconﬁrmed

in10individuals,thusestimatingaprevalenceof5.21%(95% CI2.03–8.38).ThecultureandPCRwerepositiveforB. pertus-sisin onepatient(Table1)and allconﬁrmed casesbyPCR

epidemiologicallymettheclinicalcriteriafordeﬁningacase

ofpertussis.Theclinicalcharacteristicsandepidemiological

descriptionsofthe10pertussisconﬁrmedcasesareinTable2.

Amongstthe10conﬁrmedcasesofpertussis,ﬁvewere

pri-marycases,fourwereco-primaryandonewassecondary.Of

these,ﬁvewereindexcasesthatledtotheidentiﬁcationof

ﬁvenewcases.

Discussion

Onein20casesofprolongedcoughwasfoundtohave

per-tussis. This study was conducted during an interepidemic

period.16 _This_fact _may _possibly_have_inﬂuenced _the

num-ber ofindividuals eligible for the study and inestimating

theprevalenceofpertussis.Themeanageoftheindividuals

withacoughformorethan14dayswas40.7years.Studies

undertakeninCanada,DenmarkandFrancereportedamean

age ofbetween 41and 49years.Inthe presentstudy,only

10patientswereabletoinformwhethertheyhadtakenDPT

vaccineagainstpertussis.Ofthese,onewasdiagnosedwith

pertussisbycultureandPCRandtheothersbyPCR.Asthe

par-ticipantsofthisstudywereagedover10years,theﬁnaldose

ofthevaccineforpertussiswouldhavebeenappliedatleast8

yearspreviously.Thepertussis vaccinewasﬁrstintroduced

into the Brazilianvaccine programin1983and since2003;

vaccinecoverageforthreedosesofthevaccinehasremained

above95%.16_In_around_90%_of_the_suspected_cases,_the_cough

hadlastedforaperiodof14–21daysand110(57.29%)metthe

clinicalcriteriaforpertussis.Gilbergetal.,inFrance,during

aperiodoflowprevalenceofpertussis,reportedthat79%of

conﬁrmedcasesmettheclinicalcriteria.Strebel,intheUS,

observedthat85%ofconﬁrmedcasesofpertussismet

clini-calcriteria.12_The_high_prevalence_of_cases_that_met_clinical

criteriamay beexplainedbythe factthatthosewithmore

severesymptomsweremorelikelytoseekmedicalcare.This

inturn,couldexplainwhytheprevalenceofpertussisin

ado-lescentsandadultswhopresentcoughastheonlysymptom

isunderestimated.Cultureonlyconﬁrmedthe diagnosisin

just oneoftheten patientswithpertussis (10%). PCR

con-ﬁrmed100%ofthecases.Severalstudieshavedemonstrated

lowculturesensitivityforconﬁrmingacaseofpertussisas

comparedtoPCRandbloodtests.14,16,19_The_patients_included

inthepresentstudyhadcoughformorethan14days.Itis

believedthatthetimingofculturecollectionandthe

techni-caldifﬁcultiesinvolvedinconductingthetestcontributedto

thelowsensitivityofthestudy.Thepresentstudyestimateda

prevalenceofpertussisof5.21%inadolescentsandadultswith

coughformorethan14days.StudiesconductedinAustralia,

Canada, Denmark, France and the US reported prevalence

rangingfrom10%to32%.8,9,11_As_this_study_was_carried_out

duringaninterepidemicperiod,didnotuseserologyto

con-ﬁrmthediagnosis,andthatthematerialforthecultureand

PCRwascollectedbetween14and30daysaftertheonsetof

cough,mayhaveunderestimatedtheprevalenceofpertussis

resultinginalowerprevalencethanthatinothercountries.

Thehighprevalencefoundisrelevantbecauseadultsand

ado-lescentsare themainsourceofinfectionforinfantsunder

1yearofage,theagewhenpertussishasthehigherrateof

complicationsanddeath.1,3,5–7

Table2–Clinicalandepidemiologicalcharacteristicsofadolescentsandadultswithaprolongedcoughanddiagnosed withpertussis.

Cases 1 2 3 4 5 6 7 8 9 10

Sex F F F M M F F M F M

Age(years) 28 14 20 43 43 45 15 29 34 24

Dayswithcough 18 14 15 20 14 14 14 15 14 18

Paroxysm + + + + + + + + + + Whoop − + + + + + + + + + Cyanosis − − − − − − + + − − Apnea + − − − − − + + + + Post-tussivevomiting + + + + + − − − − − Vaccinationa ₃ ₁ ₂ ₃ ₃ ₃ ₁ ₃ ₃ ₃ F:female;M:male.

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46 Conclusion

Eveninaninterepidemicperiod,pertussiswasshowntocause

onein20casesofprolongedcoughinadolescentsandadults.

Recommendation

Pertussisisunderdiagnosedamongadolescentsand adults.

Health professionalsshould bemore aware and havehigh

indexofsuspiciontorecognizepertussis ascauseofcough

illness,evenintheabsenceoflocaloutbreak.The

implemen-tationofadolescentsandadultsimmunizationcouldprotect

theinfants.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgement

WearegratefultotheLaboratórioMarceloMagalhãesfor

con-ductingthePCRsforthisstudy.

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