Rev. Bras. Hematol. Hemoter. vol.37 número3

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w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Original

article

Socioeconomic

and

demographic

characteristics

of

sickle

cell

disease

patients

from

a

low-income

region

of

northeastern

Brazil

Thales

Allyrio

Araújo

de

Medeiros

Fernandes

a,∗

,

Tereza

Maria

Dantas

de

Medeiros

b

,

Jayra

Juliana

Paiva

Alves

b

_,

_Christiane

_Medeiros

_Bezerra

b

_,

_José

_Veríssimo

_Fernandes

b

_,

Édvis

Santos

Soares

Serafim

c

_,

_Maria

_Zélia

_Fernandes

d

_,

_Maria

_de

_Fatima

_Sonati

e

a_Universidade_do_Estado_do_Rio_Grande_do_Norte_(UERN),_Mossoró,_RN,_Brazil b_Universidade_Federal_do_Rio_Grande_do_Norte_(UFRN),_Natal,_RN,_Brazil c_Hemocentro_Dalton_Cunha_(HEMONORTE),_Natal,_RN,_Brazil

d_Hospital_Infantil_Varela_Santiago,_Natal,_RN,_Brazil

e_Universidade_Estadual_de_Campinas_(UNICAMP),_Campinas,_SP,_Brazil

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Articlehistory:

Received27October2014 Accepted27February2015 Availableonline14April2015

Keywords:

Anemia Sicklecell

Socioeconomicfactors Hydroxyurea

Vaccination Penicillin

a

b

s

t

r

a

c

t

Objective:Tocharacterizethesocioeconomicanddemographicaspectsofsicklecelldisease patientsfromthestateofRioGrandedoNorte(RN),NortheastBrazil,andtheiradherence totherecommendedtreatment.

Methods:Thiscross-sectionaldescriptivestudywasperformedatreferralcentersforthe treatmentofhematologicaldiseases.Onehundredandfifty-fiveunrelatedindividualswith sicklecelldiseasewhowenttothesecentersforoutpatientvisitswereanalyzed.Allthe patients,ortheircaregivers,wereinformedabouttheresearchproceduresandobjectives, andansweredastandardizedquestionnaire.

Results:The patients were predominantly younger than 12 years old, self-declared as mulatto,livedinsmalltownsfairlydistantfromthereferralcenter,andhadlow educa-tionandsocioeconomiclevels.Individualswhoweretenor youngerwerediagnosedat anearlierage.Almost50%ofthepatientsweretakinghydroxyurea,91.4%reported hav-ingreceivedpneumococcal/meningococcalvaccinationsand76.1%receivedpenicillinas antibioticprophylaxis.However,themajorityofthemreportedhavingdifficulties follow-ingtherecommendationsofthephysicians,mainlyinrespecttoattainingtheprescribed medicationsandtransportationtothereferralcenters.

Conclusion:Theseindividualshaveavulnerablesocioeconomicsituationthatcanleadto anaggravationoftheirgeneralhealthandthusdeservespecialattentionfromthe med-icalandpsychosocial perspectives.Thus,itisnecessarytoimprovepublicpoliciesthat provideBraziliansicklecelldiseasepatientswithbetteraccesstomedicaltreatment,living conditions,andintegrationintosociety.

∗ _{Corresponding}_author_at_:_Rua_Miguel_Antônio_da_Silva_Neto,_S/N,_Aeroporto,_59607-030_Mossoró,_RN,_Brazil. E-mailaddress:thalesallyrio@yahoo.com.br(T.A.A.d.M.Fernandes).

http://dx.doi.org/10.1016/j.bjhh.2015.03.013

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Introduction

Sicklecelldisease(SCD)isoneofthemostcommonsevere monogenicdisordersworldwide.1 _The_underlying_molecular

defectisasinglenucleotidesubstitution(␤S–HBB;GAG>GTG; glu→val;rs334)inthegenethatencodesthe␤-globinchain ofhemoglobin.TheresultinghemoglobinS(HbS)polymerizes whendeoxygenated,causing polymer-associatedlesions of theredbloodcells.1,2_SCD_includes_several_different_genotypes

includingsicklecellanemia(HbSS)andcompound heterozy-gotesofHbSwith␤-thalassemia(HbS/␤-thal)orwithother typesofhemoglobinopathies.3

TheWorldHealthOrganizationrecognizedSCDasaglobal publichealthproblem,astheoverallnumberofbabiesborn withSCDbetween2010and2050isestimatedatabout14.24 million.4 _Data _from _the _Ministry _of _Health _estimates _that

around3500childrenarebornwithsicklecellanemiaeach year in Brazil and the number of cases of the disease is between25,000and30,000.5

Thecomplicationsofthisdiseasearenumerousandcan affecteveryorganandtissueinthebody.Themostcommon complicationsarepaincrises,chronicanemiaanditsacute exacerbations,stroke,acutechest syndrome,infection, pri-apism,legulcerations,osteonecrosis,andcardiacandrenal problems.6_{Complications}_can_be_acute,_producing_dramatic

clinicalfindings,orchronic,disabling,andcausepremature death.2

Specificphenotypicmanifestationsofthediseasevary con-siderablyinfrequencyandseveritybetweenpatientsandeven inthesamepatientovertime.6_Both_genetic_and_acquired

fac-torscontributetothisclinicalvariation.Amongtheacquired factors,the mostimportant isthe patient’s socioeconomic conditions.7

Knowledgeofthedemographicandsocioeconomicprofile ofSCD patientsisessentialtoidentifytheirneeds,to con-tributeto improving resource allocation and tocreate and implementpublichealthpoliciesthatbenefitthispopulation.8

However,studiesthat address theseaspectsofthe disease arerelatively scarceinboththeBrazilianandinternational literature.

Thus,thisstudy aimedtocharacterizethedemographic andsocioeconomicaspectsofSCDpatientsfromthestateof RioGrandedoNorte(RN),asocioeconomicvulnerableareaof northeasternBrazil,andtheiradherencetotherecommended treatment.

Methods

Across-sectionaldescriptive studywasperformed at refer-ralcentersforthetreatmentofhematologicaldiseasesinRN: HemocentroDalton Cunha (Natal), Hospital Infantil Varela Santiago(Natal),andtheCentrodeOncologiaeHematologia deMossoró(Mossoró).TheparticipantswereunrelatedSCD patientswithout cognitive impairment,who went tothese centersfromMarch2011toOctober2013foroutpatientvisits. Allthepatients,ortheircaregivers,wereinformedabout theresearchproceduresandobjectives,andthosewhoagreed toparticipateinthestudysignedaninformedconsentform andansweredastandardizedquestionnaire.Whenthepatient

wasyoungerthan18yearsold,itwasansweredbythe care-giver.

Thequestionswereorallyaskedbytheinterviewer with-outinducingresponses.Questionsaimedtocollectmedical historyandthedemographicandsocioeconomicdataofthe patient,includingage,ethnicity,ancestry,residence, school-ing,employmentsituation,familyincome,ageatdiagnosis, use ofhydroxyurea, prophylactic penicillin, immunization, anddifficultiesinfollowingtreatment,amongothers. Clini-callyrelevantdatawerealsotakendirectlyfromthepatient’s healthrecords.

Data were collected in singleindividual interviews, and aftercollectiontheywereinputinto aMicrosoft Excel2010 spreadsheet.Frequencydistributiontableswereusedforthe descriptive analysisofthe categoricalor nominalvariables andthesignificanceofdifferencesbetweenclinical character-isticsbyagegroupwereestimatedusingtheChi-squared(2)

orFisherexacttest,asappropriate.Thecomparisonoftheage atdiagnosisofSCDinagegroupsemployedtheKruskal–Wallis analysisofvariance(ANOVA)test,followedbymultiple com-parisonsofmeanranks,usingtheStatisticasoftware(version 7).Differenceswithap-value≤0.05wereconsidered statisti-callysignificant.

ThisstudywasconductedinaccordancewiththeHelsinki Declaration as revised in 2008, and was approved by the Research Ethics Committeeofthe Universidade Federaldo RioGrandedoNorte(UFRN,underprotocolnumber 193/09) accordingtoresolution196/96ofthe ConselhoNacionalde Saúde,Brazil.

Results

Onehundredandseventy-sevenpatientswithclinicaland lab-oratorydiagnosisofSCDwereinterviewed.However,22were first-orsecond-degreerelativesofotherpatientsparticipating inthestudyandwerethereforeexcludedfromtheanalysis. Amongtheremaining155individuals,109(70.3%)hadHbSS, 23(14.8%)wereheterozygousforHbSand␤-thalassemia,21 (13.5%)wereheterozygousforHbSandHbC,andtwo(1.3%) presentedtheassociationbetweenHbSandhereditary per-sistenceoffetalhemoglobin(HPFH).

Theagesofthepatientsrangedfromsevenmonthsto48 years,withamedianageof12years;thehighestfrequency ofindividualswasintheagegroup≤5years(29.0%),followed bythe11-to15-year-oldgroup(18.7%).Themajorityofthe individualswere male(52.9%),andself-declaredasmulatto (65.8%), but with noinformation about their ethnic ances-try (83.9%).However,indigenousancestrywaspredominant (12.3%)amongpatientswhoinformedtheirancestry.Ahigh percentageofthepatients(43.2%)livedinsmalltowns,atleast 60kmawayfromthereferralcenters(Table1).

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Table1–Demographiccharacteristicsofsicklecell diseasepatients.

Demographiccharacteristic n(%)

Agegroup(years)

≤5 45(29.0)

6–10 22(14.2)

11–15 28(18.7)

16–20 23(14.2)

21–30 23(14.8)

31 14(9.0)

Gender

Male 82(52.9)

Female 73(47.1)

Ethnicity

White 46(29.7)

Mulatto 102(65.8)

Black 7(4.5)

Ancestrya

African 10(6.5)

Indigenous 19(12.3)

European 4(2.6)

Didnotknow 130(83.9)

Residence

Natal 45(29.0)

OthertownsinNatalMetropolitanregion 27(17.4)

Mossoró 16(10.3)

OthertownsofRioGrandedoNorte 67(43.2)

a _Four _patients_reported _having_indigenous_and_African

ances-try,threereportedindigenousandEuropean,andonereported AfricanandEuropeanancestry.

thegovernment.Amongthosewhodidreceivebenefits,the Program of Continuous Cash Benefit for Social Assistance (BPC-LOAS)wasthemostprevalent(37.4%–Table2).

Themedian age atdiagnosis ofSCD was eight months (minimum: one month; maximum: eight years), two years (minimum:onemonth;maximum:14 years)andfiveyears (minimum:onemonth;maximum:47years)forindividualsin theunder11-year-old,11-to20-year-old,andover20-year-old agegroups,respectively.Astatisticallysignificantdifference wasobservedinthemedianageatdiagnosisofSCDbetween agegroups(Figure1).

60

50

40

30

P<.0001∗ P<.0001∗

P=.0001∗ P<.06812∗

20

10

0

≤10 11-20

Age of diagnosis (years)

Age group (years)

≥21

Figure1–Medianageatdiagnosisofsicklecelldisease stratifiedbyagegroup.

Table2–Socioeconomiccharacteristicsofthepatients withsicklecelldiseaseanalyzedinthisstudy. Socioeconomic

characteristic

Numberofpatients(%)

<18yearsa _≥₁₈_years _Total

Schoolinga

NeverStudied 5(4.8) 3(5.8) 8(5.2) Incomplete

primaryschool

35(34.0) 15(28.8) 50(32.3)

Complete primaryschool

26(25.2) 9(17.3) 35(22.6)

Complete secondary education

31(30.1) 24(46.1) 55(35.5)

Complete higher education

3(2.9) 1(1.9) 4(2.6)

Didnotanswer 3(2.9) – 3(1.9)

Employmentsituationa

Working 57(55.3) 14(26.9) 71(45.8) Notworking 22(21.4) 26(50.0) 48(31.0) Other 24(23.2) 12(23.0) 36(23.2)

HouseholdIncome(Brazilianminimumwage) Upto1 81(52.3) From1to2 13(8.4) From2to3 53(34.2) Morethan3 8(5.2)

Benefitsfromthefederalgovernmentb

BPC-LOAS 58(37.4) Family

allowance

51(32.9)

Others 8(5.2)

Didnotreceive socialbenefits

53(34.2)

a _The_schooling_and_employment_situation_of_the_caregivers_was

considered.

b ₁₅_patients_received_both_Program_of_Continuous_Cash_Benefit_for

SocialAssistance(BPC-LOAS)andfamilyallowance.

Themajorityofthepatients(50.3%)reportedhaving diffi-cultiesfollowingtherecommendationsofthephysicians,in particulardifficultiestoacquiretheprescribedmedications, especially hydroxyurea, and transportation to the referral centerswhenneeded(Table3).

Regarding the use of preventive measures against clin-ical complications, it was observed that hydroxyurea was

Table3–Majordifficultiesreportedbypatientstofollow prescribedtreatment.

Treatmentdifficulty n(%)

Achievetheprescribedmedication 49(31.6)

Transporttoreferralcenters 27(17.4)

Others 13(8.4)

Didnothavedifficulties 77(49.7)

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Table4–Useofpreventivemeasuresagainstclinicalcomplications,accordingtoagegroup. UseofHydroxyurea

n(5)

Vaccinationsb n(5)

Prophylacticuseofpenicillin n(5)

Yes No Yes No Yes No

Agegroup(years)

≤5 5(11.1) 40(88.9) 42(93.3) 3(6.7) 43(95.6) 2(4.4) 6–10 13(59.1) 9(40.9) 22(100.0) 0(0.0) 21(95.5) 1(4.5) 11–15 16(57.1) 12(42.9) 28(100.0) 0(0.0) 20(71.4) 8(28.6) 16–20 9(39.1) 14(60.9) 20(95.2) 1(4.8) 15(65.2) 8(34.8) 21–30 15(65.2) 8(34.8) 18(78.3) 5(21.7) 15(65.2) 8(34.8) 31 9(64.2) 5(35.7) 8(66.7) 4(33.3) 4(28.5) 10(71.4)

Total 67(43.2) 88(56.8) 138(91.4) 13(8.6) 118(76.1) 37(23.9)

p-value 0.000a _0.002a _0.000a

p-valueComparisonoftheuseofpreventivemeasuresamongtheagegroupscalculatedbyFisherExacttest. a _{Statistically}_significant.

b _{Pneumococcal/meningococcal}_vaccinations_(Four_patients_did_not_remember_if_they_had_ever_received_pneumococcal_{vaccinations).}

regularlyusedby43.2%ofthepatients,withthispercentage being significantly lower in the youngest age group. Fur-thermore,itwasfoundthatthemajority(91.4%)ofpatients reportedhavingreceivedpneumococcal/meningococcal vac-cinations and penicillin as antibiotic prophylaxis (76.1%). However,thesepercentagesweremuchlowerintheoldestage groupanditwasnotpossibletoverifywhetherthevaccination wascompleteorincompleteforallpatients(Table4).

Discussion

SCD is achronic, degenerative and self-incapacitating dis-easeaffectingthepatientandtheirfamilyinanintenseand permanent way. The clinical complications and the recur-renthospitalizationsandbloodtransfusions,associatedwith externaldomainssuchasunemployment,lowincome,and lackofaccesstohealthservices,negativelyinfluencethelife ofthispopulation.7

Peopleinavulnerablesocioeconomicsituation aremore exposed to the determining social factors of the disease, which can lead to an aggravation of the patients’ general health.Therefore,theseindividualsdeservespecialattention inrespecttomedicalandpsychosocialperspectives.9

RioGrandedoNorteisalow-incomeareaofBrazil, hav-ingaHumanDevelopmentIndexof0.684(16thofallBrazilian states),10_an_illiteracy_rate_of_19.8%,_and_a_child_mortality_of

17.0%.Moreover,62.6%offamilieshaveamonthlypercapita incomeofuptooneminimumwage(aboutUS$240.00).11

Inthisstudy,patientswerepredominantlyyoungerthan 12years,self-declaredasmulattoandlivingintownsfairly distant from referral centers for the treatment of SCD. Additionally,morethanonethirdofthepatients,ortheir care-givers,hadonlyfinishedelementaryschool,werenotworking, hadaverylowhouseholdincome,andwerenotreceivingany socialbenefitsfromthegovernment.

Theagegroupprofileofthisstudywassimilartothatfound byMaximo12_in_Rio_de_Janeiro,_Brazil._The_predominance_of

childrenandadolescentsseemstodemonstratetheseverity ofthedisease,withpatientspresentinglowlifeexpectancy, despiteimportantadvancesthatemergedinthelastdecades

forthepreventionandtreatmentofcomplicationsofthe dis-ease.

Thepredominanceofmulattoesamongpatientsisrelated to theethnic background ofthe populationofthe stateof RioGrandedoNorte accordingtothe BrazilianInstituteof Geography and Statistics (IBGE),11 _where _the _influence _of

AfricanslaveswasnotsostrongasinsomeotherBrazilian states.13_The_predominance_of_indigenous_ancestry_among_the

patientswhoinformedanyancestrycorroboratesthis hypoth-esis.However,manystudiesworldwidehaveshownthatSCD is more common in individuals ofblack ethnicity, that is, Africandescent.5,14_Therefore,_it_is_likely_that_the_distribution

ofthisself-reportedethnicitymayhavebeeninfluencednot onlybythehighdegreeofmiscegenation,butalsobyacertain degreeofbiasoftheindividualsanalyzed,whooftenpreferto declarethemselvesasmulattoesinsteadofBlacks.

The low education level and socioeconomic status of the patients were similar to those found in studies con-ductedinEngland,15_the_USA,16_Nigeria17_and_other_states_of

Brazil.7,8,18,19_This_generates_a_condition_of_social

vulnerabil-itythataffectsthequalityoflifeofpatientsandmakesthem moredependentongovernmentprogramsforfinancial bene-fitsand healthcare.Additionally,onethirdoftheanalyzed patients were notreceiving any social benefits,asituation thatimpairstheirlivingconditionsevenfurther.These vul-nerableconditionsalsoinfluenceadherencetothetreatment recommendedbythephysician.20

Despite the complexity and multifactorial pathophysi-ology of the disease, relatively straightforward measures have greatly improved outcomes for children with SCD. SuchmeasuresincludeearlyidentificationofSCDby neona-tal screening programs and the prompt establishment of preventivemeasureswithprophylacticpenicillinand immun-izations,andtherapeuticinterventions,suchastransfusions andhydroxyurea.21

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ishigherthan that reportedbyother studies conductedin Brazil18,22 _and _the _USA,23,24 _and _demonstrates_good

adher-enceofthepatientstotreatmentandthehealthcareteam’s confidence in the efficacy of the medicine. However, only 11% ofunder 5-year-old childrenwere takinghydroxyurea, whichseemstoreflecttheconcernsabouttheoverallsafety ofthismedicine,mainlyinveryyoungchildren.Theresultsof thePediatricsHydroxyureaPhase3ClinicalTrial(BabyHUG) demonstrated bothsafety and beneficial effectsof hydrox-yureainasymptomaticandsymptomaticyoungchildrenwith SCA,andsuggeststhatcliniciansshouldconsiderchanging theirpracticetoprescribe hydroxyureatherapy forallvery youngchildrenwithSCA,ratherthantreatingonlythosemost severelyaffected.25

Theratesofvaccination (91.4%)andprophylacticuse of penicillin(76.1%)foundinthisstudyalsodemonstrategood adhesionofhealthstaffandpatientstogeneral recommen-dations forthe treatment of SCD. Improved immunization against Streptococcus pneumoniae and Haemophilus influenza, and the use of penicillin prophylaxis have dramatically reducedthefrequencyofseriousbacterialinfectionsand mor-talityofinfantswithSCA.26,27

ThisimmunizationcoverageofpatientswithSCDwas sim-ilartothoseobtainedbyFrauchesetal.28_in_the_state_of_Espírito

Santo,Brazil,andbyHardieetal.29_in_patients_from_Jamaica.

On the other hand, the prophylactic use ofpenicillin was higherthantheratereportedbyWarrenetal.30_in_the_USA,

andsimilartothosedescribedinothersstudiescarriedoutin Brazil31_and_Jamaica.32_However_it_was_not_possible_to_directly

assessthevaccinationrecordcardofallindividuals,nor ver-ifyadherencetoprophylacticpenicillinbyothermethods;it ispossiblethatourresultsareoverestimated.Lowerratesof adherencetothesepracticesintheolderagegroupscanbe explainedbythefactthattheserecommendationswere estab-lishedinthe1980sand1990s.

Despitethis adherence totreatmentand use of preven-tive measures, a significant percentage (31.6%) ofpatients reportedproblemsinachievingtheprescribed medications, especiallyhydroxyurea.Thehighcostsofthesemedicinesand lowsocioeconomicstatusofpatientsmakethemdependent onpublicprogramsfordispensingmedicines.Therefore,the occurrenceoffinancialandadministrativeproblemsinthese programscanmakeaccesstotherecommendedtherapyquite difficult.

Thedistancetoreferencecentersconstitutesabarrierto the implementation of a comprehensive care program for SCDpatients,asitgenerallyrestrictstransportationtohealth services.33_Added_to_this,_the_need_to_travel_to_get_treatment

endangers patients’ lives.Astudy conductedbyFernandes andViana34_pointed_out_difficulties_in_getting_{transportation}

tothehealthcenter asacontributingfactor forpremature deathsoftheseindividuals.Inourstudy,almosthalfofthe analyzedindividuals lived intowns fairlydistant from the referralcentersand17.4%reporteddifficultiesinarrivingat thecenterstoperformtherecommendedtreatment.

Therefore, it is necessary toimprove publicpolicies for theseindividuals,takingintoaccounttheirlowsocioeconomic status,demographiccharacteristics,anddifficultiesin achiev-ingtherecommendedtreatment.Andtobeeffective,these measuresneedtoprovidepsychosocialcounselingnecessary

forthedevelopmentofthepatient’sintegrationintosociety, as well as accessto medicaltreatment, allowingfavorable improvementsintherealityexperiencedbyBrazilianswith thisdisease.

Certainlimitations ofthecurrent studyshouldbetaken intoaccount,especiallywithregardtoadherencetothe rec-ommended medical treatment. As it was not possible to analyzethevaccinationrecordcardsofallpatients,wewere notabletoassesstheadequacyofthevaccineprogram. Fur-thermore,theuseofhydroxyureaandprophylacticpenicillin wasevaluatedtakingintoaccountonlythepatients’reports. Therefore,theirregularandproperuseofthesedrugscould notbeproven.

Conclusions

SCD patients from the state of Rio Grandedo Norte have a vulnerable socioeconomic situation that can lead to an aggravation oftheir generalhealthand thus deserves spe-cialattentionfromthemedicalandpsychosocialperspectives. Therefore, it is necessary to improve public policies that provide BrazilianswithSCDbetteraccesstomedical treat-ment,livingconditions,andintegrationintosociety.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

Thisstudy wassupportedbyConselhoNacionalde Desen-volvimento Científico e Tecnológico (CNPq, grant no. 402022/2010-6) and Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant no. 08/57441-0). We would liketothankthestaffofHemocentroDaltonCunha, HospitalInfantilVarelaSantiago,andCentrodeOncologiae HematologiadeMossorófortheaccessprovidedtopatients.

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