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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A vasculopatia livedoide &#40;VL&#41; manifesta&#8208;se como &#250;lceras dolorosas localizadas distalmente nos membros inferiores que evoluem lentamente para les&#245;es atr&#243;ficas esbranqui&#231;adas&#44; com telangiectasias puntiformes&#44; pigmenta&#231;&#227;o acastanhada&#44; acompanhadas de livedo racemoso&#46; A etiopatogenia mais aceita da VL s&#227;o fen&#244;menos vaso&#8208;oclusivos decorrentes de estados de hipercoagulabilidade&#46; Condi&#231;&#245;es como trombofilia&#44; colagenoses&#44; doen&#231;as mieloproliferativas e estase sangu&#237;nea s&#227;o reconhecidamente associadas &#224; doen&#231;a&#44; por&#233;m a forma idiop&#225;tica &#40;prim&#225;ria&#41; &#233; a predominante&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Este estudo foi realizado a partir da observa&#231;&#227;o cl&#237;nica de paciente do sexo feminino de 41 anos&#44; com hist&#243;ria de contato com gatos e que apresentava les&#245;es ulceradas dos membros inferiores de dif&#237;cil controle havia 12 anos &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 e 2</a>&#41;&#46; O exame anatomopatol&#243;gico evidenciou hipodermite em atividade associada &#224; vasculite leucocitocl&#225;stica e presen&#231;a de trombos hialinos frequentes&#44; com necrose fibrinoide da parede de pequenos vasos&#46; Observou&#8208;se tamb&#233;m dep&#243;sito de mucina e de hemossiderina&#44; al&#233;m de prolifera&#231;&#227;o vascular &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; Exclu&#237;das outras doen&#231;as&#44; a paciente foi conduzida como VL prim&#225;ria e tratada&#44; ao longo dos anos&#44; com vasodilatadores&#44; antiagregantes plaquet&#225;rios&#44; corticosteroides e ciclos de antibi&#243;ticos &#40;metronidazol&#44; penicilina e ciprofloxacina&#41;&#44; com melhoras transit&#243;rias&#46; Considerada a forte epidemiologia de contato com gatos&#44; foi sugerida a pesquisa de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; O DNA de <span class="elsevierStyleItalic">Bartonella henselae</span> foi detectado por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41; no sangue da paciente&#44; e houve pronta melhora das &#250;lceras cr&#244;nicas com o tratamento da infec&#231;&#227;o por <span class="elsevierStyleItalic">B&#46; henselae</span> com doxiciclina 200 mg&#47;dia por um ano&#46; Com a suspens&#227;o do tratamento&#44; por&#233;m&#44; houve recorr&#234;ncia das les&#245;es de VL&#46; A bact&#233;ria pode ser isolada&#44; e seu DNA novamente detectado a partir de nova amostra sangu&#237;nea &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Bartonella</span> spp&#46; s&#227;o bact&#233;rias fastidiosas e&#44; por isso&#44; dificilmente isoladas&#46; Embora mundialmente distribu&#237;das&#44; s&#227;o negligenciadas e potencialmente fatais&#46; Muitas vezes vivem no interior de eritr&#243;citos e de c&#233;lulas endoteliais&#46; A infec&#231;&#227;o por essas bact&#233;rias pode ser assintom&#225;tica&#44; mas tamb&#233;m pode causar quadros cl&#237;nicos variados em humanos&#44; incluindo febre de origem indeterminada&#44; endocardite e doen&#231;a da arranhadura do gato &#40;DAG&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> As manifesta&#231;&#245;es cut&#226;neas tamb&#233;m variam e incluem vasculite leucocitocl&#225;stica e &#250;lceras&#44; como revisto por Lins et al&#46; em recente revis&#227;o sobre as manifesta&#231;&#245;es cut&#226;neas das bartoneloses publicada neste peri&#243;dico&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> O objetivo principal deste estudo foi investigar a bacteremia por <span class="elsevierStyleItalic">Bartonella</span> spp<span class="elsevierStyleItalic">&#46;</span> em pacientes com VL prim&#225;ria com &#250;lceras de dif&#237;cil controle&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Foi obtido o Termo de consentimento livre e esclarecido de cada participante ap&#243;s avalia&#231;&#227;o e autoriza&#231;&#227;o do Comit&#234; de &#201;tica em Pesquisa da Universidade Estadual de Campinas &#8211; Unicamp &#40;CAAE&#58; 48163015&#46;8&#46;0000&#46;5405&#41;&#46; Foram inclu&#237;dos pacientes com mais de 18 anos&#44; com diagn&#243;stico de VL prim&#225;ria em seguimento no Ambulat&#243;rio de Dermatologia da Unicamp e volunt&#225;rios sem queixas cl&#237;nicas como grupo controle &#40;estudantes e&#47;ou funcion&#225;rios da Unicamp&#44; com mais de 18 anos e n&#227;o gestantes&#41;&#46; Cada participante respondeu a um question&#225;rio para avaliar a exposi&#231;&#227;o de risco para adquirir a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; Foram coletadas amostras de sangue dos pacientes e dos indiv&#237;duos do grupo controle com t&#233;cnica ass&#233;ptica em tubos com &#225;cido etilenodiamina tetra&#8208;ac&#233;tico &#40;EDTA&#41; e em tubos sem anticoagulante&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O laborat&#243;rio onde as an&#225;lises foram realizadas segue normas para assegurar o controle de qualidade descrito por Pitassi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Foram realizadas culturas l&#237;quidas de amostras do sangue e do <span class="elsevierStyleItalic">pellet</span> de c&#233;lulas &#40;co&#225;gulo de sangue coletado do tubo sem coagulante&#41; e culturas s&#243;lidas de todas as culturas l&#237;quidas&#44; conforme descri&#231;&#227;o pr&#233;via&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a> O DNA foi extra&#237;do de amostras sangu&#237;neas&#44; dos <span class="elsevierStyleItalic">pellets</span> de c&#233;lulas e das culturas l&#237;quidas utilizando QIAamp DNA <span class="elsevierStyleItalic">minikit</span> &#40;Qiagen Inc&#46;&#44; EUA&#41;&#46; Al&#233;m de PCR convencional para gene constitutivo de mam&#237;feros&#44; o GAPDH&#44; foram realizadas PCR convencional g&#234;nero&#8208;espec&#237;fica para <span class="elsevierStyleItalic">Bartonella</span> spp&#46; e PCRs esp&#233;cie&#8208;espec&#237;ficas de dupla amplifica&#231;&#227;o &#40;<span class="elsevierStyleItalic">nested</span>&#41; e em tempo real para <span class="elsevierStyleItalic">B&#46; henselae</span>&#46; Em todos os procedimentos foram adicionados tr&#234;s controles &#40;controle negativo de extra&#231;&#227;o&#44; controle negativo de PCR e controle positivo de PCR &#8208; cepa 3715 de <span class="elsevierStyleItalic">B&#46; henselae</span> registrada na Se&#231;&#227;o de Cole&#231;&#227;o de Culturas do Instituto Adolfo Lutz&#41;&#46; Al&#233;m disso&#44; em cada rea&#231;&#227;o foram testadas dilui&#231;&#245;es de <span class="elsevierStyleItalic">B&#46; henselae</span> para determinar a sensibilidade e o limite de detec&#231;&#227;o de cada PCR&#46; Todos esses m&#233;todos j&#225; foram descritos anteriormente&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;11</span></a> Os <span class="elsevierStyleItalic">primers</span> utilizados na investiga&#231;&#227;o molecular dos pacientes e volunt&#225;rios est&#227;o descritos na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Os amplificados obtidos que apresentaram qualidade para o sequenciamento foram enviados para compara&#231;&#227;o de similaridade com material depositado previamente&#46; O fluxograma dos procedimentos realizados est&#225; apresentado na <a class="elsevierStyleCrossRef" href="#fig0020">figura 4</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0030" class="elsevierStylePara elsevierViewall">Participaram do estudo 16 pacientes com VL prim&#225;ria e 32 indiv&#237;duos sem queixas cl&#237;nicas&#46; Todos responderam a um question&#225;rio cujos dados s&#227;o apresentados na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; Pode&#8208;se observar que o grupo controle era mais jovem &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; com m&#233;dia et&#225;ria de 26&#44;71 anos&#59; j&#225; entre os pacientes&#44; a m&#233;dia foi de 37&#44;62 anos&#46; O grupo controle foi composto por mais homens que o grupo dos pacientes &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;048&#41;&#46; Os indiv&#237;duos do grupo controle tiveram mais contato com animais de cria&#231;&#227;o &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#44; foram mais mordidos e&#47;ou arranhados &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#41; e foram mais expostos a artr&#243;podes &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#41;&#46; N&#227;o houve diferen&#231;a significante &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05&#41; na compara&#231;&#227;o entre essas caracter&#237;sticas dentre aqueles que tiveram detec&#231;&#227;o do DNA de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; e os que n&#227;o tiveram&#44; em cada um dos grupos separadamente&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">O gene constitutivo &#40;GAPDH&#41; foi detectado em todas as amostras de pacientes e volunt&#225;rios&#44; garantindo a qualidade do DNA extra&#237;do para as an&#225;lises e a aus&#234;ncia de inibidores para as rea&#231;&#245;es moleculares&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Na PCR convencional para <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; o limite de detec&#231;&#227;o foi de 50 c&#243;pias&#44; e de 10 c&#243;pias na PCR <span class="elsevierStyleItalic">nested</span> e na PCR em tempo real&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O DNA de <span class="elsevierStyleItalic">B&#46; henselae</span> foi detectado em quatro pacientes em&#44; pelo menos&#44; uma rea&#231;&#227;o esp&#233;cie&#8208;espec&#237;fica&#46; No grupo controle&#44; o DNA foi detectado em quatro volunt&#225;rios&#46; Puderam ser sequenciados os amplificados de seis participantes dos oito com detec&#231;&#227;o do DNA bacteriano&#44; e todos os amplificados apresentaram 99&#37; a 100&#37; de similaridade com <span class="elsevierStyleItalic">B&#46; henselae</span> &#40;n&#250;mero de acesso GenBank&#58; CP020742&#46;1&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">N&#227;o foi observado crescimento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em cultura s&#243;lida de nenhuma amostra dos 48 participantes&#46; N&#227;o houve signific&#226;ncia estat&#237;stica pelo teste de Fischer na detec&#231;&#227;o do DNA da bact&#233;ria entre os dois grupos &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;413&#41;&#44; como tamb&#233;m observado na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Considerando que a VL prim&#225;ria &#233; manifesta&#231;&#227;o rara&#44; e utilizando o teste exato de Fisher para estabelecer o c&#225;lculo amostral do estudo e definindo o n&#237;vel de signific&#226;ncia em 5&#37; &#40;erro alfa ou tipo I&#41; com poder amostral de 80&#37; &#40;erro beta ou tipo II de 20&#37;&#41;&#44; com base nos dados obtidos&#44; pode&#8208;se estabelecer que a amostra m&#237;nima para que os resultados tenham signific&#226;ncia estat&#237;stica seria de 106 pacientes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0060" class="elsevierStylePara elsevierViewall">N&#227;o foi encontrado pelos autores nenhum trabalho na literatura relacionando infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; &#224; VL&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Da mesma maneira que foi proposto para o SARS&#8208;CoV&#8208;2&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> &#233; poss&#237;vel que a infec&#231;&#227;o persistente por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; tamb&#233;m cause dano vascular direto ou promova estado de hipercoagulabilidade&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Sabe&#8208;se que a VL &#233; uma doen&#231;a vaso&#8208;oclusiva com hialiniza&#231;&#227;o e trombose de vasos d&#233;rmicos&#59; muitos pacientes se queixam de dor e parestesia&#46; Todos os pacientes do estudo referiram dor intensa associada &#224; presen&#231;a de &#250;lceras&#44; e a maioria referiu parestesia ou dor leve ap&#243;s a cicatriza&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> H&#225; v&#225;rios artigos que relacionam dores cr&#244;nicas &#224; infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#8211;15</span></a> Estudos translacionais documentam hipersensibilidade dolorosa em camundongos infectados com <span class="elsevierStyleItalic">B&#46; henselae</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#44;17</span></a> Esses micro&#8208;organismos causam infec&#231;&#227;o intraendotelial e poderiam estimular a s&#237;nteses de endotelina &#40;ET&#8208;1&#41;&#44; um potente vasoconstritor&#44; que &#233; relacionado &#224; parestesia e dor&#44; incluindo dor cr&#244;nica&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#44;16&#44;18&#44;19</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Em tr&#234;s quartos dos pacientes n&#227;o foi poss&#237;vel detectar o DNA de <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; o que n&#227;o surpreende&#44; j&#225; que a VL &#233; uma manifesta&#231;&#227;o cut&#226;nea de diferentes enfermidades&#46; Al&#233;m disso&#44; <span class="elsevierStyleItalic">B&#46; henselae</span> causa bacteremia c&#237;clica&#44; e as amostras sangu&#237;neas podem ter sido obtidas nos intervalos em que a bact&#233;ria n&#227;o estava circulando&#46; Diferentes autores mostram que a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; tem maior chance de ser diagnosticada por bi&#243;psia de fragmentos teciduais em vez de amostra sangu&#237;nea&#44; e que os resultados dessa diferen&#231;a podem ser de maior import&#226;ncia e signific&#226;ncia estat&#237;stica&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#8211;23</span></a> Por quest&#245;es &#233;ticas&#44; foram coletadas apenas amostras sangu&#237;neas para minimizar os danos aos volunt&#225;rios do grupo controle&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; n&#227;o h&#225; m&#233;todo padr&#227;o ouro de diagn&#243;stico para infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; e resultados falso&#8208;negativos s&#227;o frequentes&#44; mesmo quando usada plataforma com t&#233;cnicas moleculares e microbiol&#243;gicas&#46; A necessidade de m&#250;ltiplos testes para detec&#231;&#227;o adequada desse micro&#8208;organismo visando reduzir falso&#8208;negativos j&#225; foi discutida por Drummond et al&#46; As t&#233;cnicas moleculares t&#234;m como limita&#231;&#227;o baixa sensibilidade &#40;m&#237;nimo de 4&#46;000 c&#243;pias&#47;mL no laborat&#243;rio onde foram realizadas as an&#225;lises&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Mesmo em doen&#231;as em que h&#225; o envolvimento tecidual&#44; a identifica&#231;&#227;o do agente no exame anatomopatol&#243;gico tem baixa sensibilidade&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Historicamente&#44; as colora&#231;&#245;es com impregna&#231;&#227;o de prata s&#227;o utilizadas para a detec&#231;&#227;o de esp&#233;cies de <span class="elsevierStyleItalic">Bartonella</span>&#59; no entanto&#44; como a colora&#231;&#227;o n&#227;o &#233; espec&#237;fica&#44; a leitura pode ser dif&#237;cil em decorr&#234;ncia da forma&#231;&#227;o de precipitado de prata&#46; Estudo de Caponetti et al&#46; avaliou o uso da imuno&#8208;histoqu&#237;mica &#40;IHQ&#41; para identifica&#231;&#227;o de <span class="elsevierStyleItalic">B&#46; henselae</span> na DAG em 24 casos de linfadenite&#44; a partir de bi&#243;psias fixadas em formalina e inclu&#237;dos em parafina&#44; e comparou os resultados com impregna&#231;&#227;o por prata &#40;IP&#41; e PCR&#46; Os casos positivos foram os seguintes&#58; IP&#44; 11 &#40;46&#37;&#41;&#59; PCR&#44; 9 &#40;38&#37;&#41;&#59; e IHQ&#44; 6 &#40;25&#37;&#41;&#46; Apenas dois casos &#40;8&#37;&#41; foram positivos para todos os tr&#234;s estudos&#46; A IP mostrou&#8208;se mais sens&#237;vel&#44; mas menos espec&#237;fica&#46; Apesar de 11 &#40;46&#37;&#41; dos casos do estudo terem sido positivos usando IP&#44; apenas seis dessas amostras foram concomitantemente positivas por an&#225;lise IHQ e&#47;ou PCR&#46; Esse achado sugere que v&#225;rios dos casos interpretados como positivos pela IP podem representar falso&#8208;positivos&#44; e que a sensibilidade diagn&#243;stica desses tr&#234;s testes &#233; baixa para DAG&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> Outro estudo com 106 casos de endocardite comparou os resultados de IHQ&#44; <span class="elsevierStyleItalic">Western blotting</span> e PCR em tempo real de sangue total&#44; soro e tecido valvar&#46; A IHQ e a colora&#231;&#227;o de Warthin&#8208;Starry foram as t&#233;cnicas menos sens&#237;veis&#46; Neste estudo&#44; a colora&#231;&#227;o de Warthin&#8208;Starry foi o mais sens&#237;vel desses dois m&#233;todos &#40;cinco amostras foram positivas para colora&#231;&#227;o de Warthin&#8208;Starry e negativas na an&#225;lise IHQ&#41;&#46; Entretanto&#44; esta colora&#231;&#227;o histol&#243;gica n&#227;o &#233; espec&#237;fica para <span class="elsevierStyleItalic">Bartonella</span> spp&#46; Como o processo infeccioso pode ser localizado&#44; um resultado imuno&#8208;histoqu&#237;mico negativo n&#227;o exclui definitivamente o diagn&#243;stico de endocardite por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> J&#225; o isolamento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; &#233; dif&#237;cil mesmo em condi&#231;&#245;es espec&#237;ficas e ideais&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">A bacteremia p&#244;de ser documentada no caso &#237;ndice&#44; pelo isolamento da bact&#233;ria em meio s&#243;lido mesmo ap&#243;s um ano de tratamento com doxiciclina&#44; mas n&#227;o houve isolamento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em nenhum dos participantes do estudo&#46; A dificuldade de tratar a infec&#231;&#227;o com antibi&#243;ticos&#44; como observado na febre das trincheiras &#40;causada por <span class="elsevierStyleItalic">Bartonella quintana</span>&#41; e na febre de Oroya &#40;que &#233; a primeira manifesta&#231;&#227;o da doen&#231;a bif&#225;sica da doen&#231;a de Carri&#243;n&#44; que pode evoluir para verruga peruana e &#233; causada por <span class="elsevierStyleItalic">Bartonella bacilliformis</span>&#41;&#44; sugerem que essas bact&#233;rias n&#227;o s&#227;o erradicadas&#46; Essa potencial persist&#234;ncia da infec&#231;&#227;o impossibilita garantir que manifesta&#231;&#245;es observadas na VL sejam rea&#231;&#245;es imunes infecciosas ou p&#243;s&#8208;infecciosas&#44; como se tem aventado&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Poucos grupos de pesquisa realizam cultura s&#243;lida para isolamento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; Isso porque o isolamento depende de meios espec&#237;ficos e incuba&#231;&#227;o prolongada&#46; Al&#233;m disso&#44; o crescimento fastidioso e a falta de sucesso no primo&#8208;isolamento fazem com que esse tipo de diagn&#243;stico n&#227;o seja vi&#225;vel&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Como a VL &#233; a express&#227;o cut&#226;nea de diferentes doen&#231;as&#44; a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; poderia ser apenas uma das causas dessa manifesta&#231;&#227;o&#46; Al&#233;m disso&#44; por infectar as c&#233;lulas endoteliais e ser o &#250;nico g&#234;nero conhecido de bact&#233;rias a estimular sua prolifera&#231;&#227;o em humanos&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> a pesquisa em amostras sangu&#237;neas pode n&#227;o representar a real condi&#231;&#227;o do paciente em rela&#231;&#227;o &#224; infec&#231;&#227;o por essas bact&#233;rias&#44; pois a bacteremia costuma ser c&#237;clica&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Dados coletados no question&#225;rio de fatores de risco para bartonelose &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41; mostraram que os volunt&#225;rios do grupo controle eram significantemente mais jovens&#44; uma vez que a maioria desses volunt&#225;rios &#233; composta por estudantes da Unicamp&#46; A VL acomete mais mulheres&#44; e houve diferen&#231;a estat&#237;stica entre a propor&#231;&#227;o dos sexos dos grupos&#46; Uma limita&#231;&#227;o do estudo &#233; que os volunt&#225;rios eram mais expostos a fatores de risco para adquirir a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; fatores esses observados em estudo realizado com doadores de sangue do Hemocentro da Unicamp&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> uma vez que relataram&#44; em maior n&#250;mero em rela&#231;&#227;o aos pacientes&#44; terem sofrido mordidas e arranhaduras&#44; contato com animais de cria&#231;&#227;o e exposi&#231;&#227;o a artr&#243;podes&#46; Mesmo com menor exposi&#231;&#227;o de risco&#44; o grupo de pacientes com VL apresentou o dobro da taxa de infec&#231;&#227;o &#40;25&#37;&#59; 4&#47;16&#41;&#44; o que pode indicar que a preval&#234;ncia da infec&#231;&#227;o por <span class="elsevierStyleItalic">B&#46; henselae</span> nos pacientes seja maior e que essas bact&#233;rias possam&#44; de fato&#44; ter rela&#231;&#227;o com o desencadeamento da doen&#231;a&#46; Outra justificativa para n&#227;o ter sido encontrada diferen&#231;a estat&#237;stica &#233; o pequeno n&#250;mero de pacientes do estudo&#44; que avalia pacientes com doen&#231;a rara e que foi realizado como piloto em uma &#250;nica institui&#231;&#227;o&#46; Como descrito nos resultados&#44; usando como controle volunt&#225;rios com as mesmas caracter&#237;sticas&#44; seria necess&#225;rio um n&#250;mero de pacientes quase sete vezes maior para documentar a signific&#226;ncia estat&#237;stica&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A inexist&#234;ncia de padr&#227;o ouro&#44; aliada &#224; grande dificuldade em se detectar a bacteremia causada por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; refor&#231;am a necessidade de se utilizar m&#233;todos diversos e complementares visando aumentar a sensibilidade e a precis&#227;o do diagn&#243;stico&#46; Essa combina&#231;&#227;o de m&#233;todos e de testagem de diferentes amostras torna o diagn&#243;stico laboratorial mais eficaz e tem sido utilizada por diferentes grupos de pesquisa&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;20&#44;28&#8211;30</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0110" class="elsevierStylePara elsevierViewall">O DNA de <span class="elsevierStyleItalic">B&#46; henselae</span> foi detectado em um de cada quatro pacientes com VL prim&#225;ria&#44; o que refor&#231;a a necessidade de investigar a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; nesses indiv&#237;duos&#44; ainda que n&#227;o tenha havido diferen&#231;a estat&#237;stica entre o grupo de pacientes e o grupo controle&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0115" class="elsevierStylePara elsevierViewall">Bolsa de Doutorado CNPq 170501&#47;2018&#8208;3 &#40;Santos&#44; LS&#41;&#59; bolsa de P&#243;s&#8208;Doutorado Fapesp 2018&#47;12565&#8208;6 &#40;Drummond&#44; MR&#41;&#59; bolsa produtividade CNPq 301900&#47;2015&#8208;9 &#40;Velho&#44; PENF&#41;&#59; Fundo de Apoio &#224; Dermatologia de S&#227;o Paulo &#40;Funadersp&#41;&#47;Sociedade Brasileira de Dermatologia&#44; Regional S&#227;o Paulo &#40;Fran&#231;a&#44; AFEC&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0120" class="elsevierStylePara elsevierViewall">Marina Rovani Drummond&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Luciene Silva dos Santos&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Lais Bomediano Souza&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Gabriela Nero Mitsuushi&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; participa&#231;&#227;o sele&#231;&#227;o dos pacientes e coleta das amostras&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Maria Let&#237;cia Cintra&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Andrea Fernandes Eloy da Costa Fran&#231;a&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Elemir Macedo de Souza&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Paulo Eduardo Neves Ferreira Velho&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o sele&#231;&#227;o dos pacientes e coleta das amostras&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflito de interesses</span><p id="par0160" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A vasculopatia livedoide &#40;VL&#41; manifesta&#8208;se como &#250;lceras e cicatrizes atr&#243;ficas nacaradas nas extremidades inferiores&#46; O principal fator etiopatog&#234;nico &#233; a hipercoagulabilidade&#44; com a forma&#231;&#227;o de trombos seguida de inflama&#231;&#227;o&#46; Trombofilia&#44; doen&#231;as do col&#225;geno e doen&#231;as mieloproliferativas podem levar &#224; VL&#44; mas a forma idiop&#225;tica &#40;prim&#225;ria&#41; predomina&#46; <span class="elsevierStyleItalic">Bartonella</span> spp&#46; podem causar infec&#231;&#227;o intraendotelial&#59; as manifesta&#231;&#245;es cut&#226;neas da infec&#231;&#227;o por essas bact&#233;rias podem ser diversas&#44; incluindo vasculite leucocitocl&#225;stica e &#250;lceras&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A partir de um caso cl&#237;nico&#44; o objetivo deste estudo foi investigar a bacteremia por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em pacientes com &#250;lceras cr&#244;nicas de dif&#237;cil controle diagnosticadas como VL prim&#225;ria&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram aplicados question&#225;rios e realizados testes moleculares &#40;PCR convencional&#44; PCR de dupla amplifica&#231;&#227;o e PCR em tempo real&#41;&#44; culturas l&#237;quidas e s&#243;lidas em amostras sangu&#237;neas e <span class="elsevierStyleItalic">pellets</span> de c&#233;lulas de 16 pacientes com VL prim&#225;ria e 32 volunt&#225;rios saud&#225;veis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O DNA de <span class="elsevierStyleItalic">Bartonella henselae</span> foi detectado em 25&#37; dos pacientes com VL e em 12&#44;5&#37; dos indiv&#237;duos do grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;413&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Pela raridade da VL prim&#225;ria&#44; o n&#250;mero de pacientes estudados foi pequeno e houve maior exposi&#231;&#227;o do grupo controle a fatores de risco para infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Embora sem diferen&#231;a estat&#237;stica significante entre os grupos&#44; o DNA de <span class="elsevierStyleItalic">B&#46; henselae</span> foi detectado em um de cada quatro pacientes&#44; o que refor&#231;a a necessidade de investigar a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em pacientes com VL prim&#225;ria&#46;</p></span>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR convencional &#40;ITS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR <span class="elsevierStyleItalic">nested</span> &#40;<span class="elsevierStyleItalic">fstZ</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR convencional &#40;ITS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR <span class="elsevierStyleItalic">nested</span> &#40;<span class="elsevierStyleItalic">fstZ&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR convencional <span class="elsevierStyleItalic">&#40;</span>ITS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR <span class="elsevierStyleItalic">nested</span> &#40;<span class="elsevierStyleItalic">fstZ&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Novembro&#47;2012 &#40;em tratamento com antibi&#243;tico&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8722;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8722;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8722;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Sem crescimento</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Sem crescimento</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dezembro&#47;2013 &#40;sem tratamento com antibi&#243;tico&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8722;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3211272.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Resultados das pesquisas moleculares no caso &#237;ndice de vasculopatia livedoide prim&#225;ria com bacteremia confirmada por <span class="elsevierStyleItalic">Bartonella henselae</span></p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Primer</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sequ&#234;ncia de nucleot&#237;deos &#40;5&#8217;&#8208;3&#8217;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alvo molecular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Convencional&#91;9&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAPDH F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCTTCATTGACCTCAACTACAT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAPDH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAPDH R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCAAACTTGTCATGGATGACC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Convencional&#91;10&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITS F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CTTCAGATGATGATCCCAAGCCTTYTGGCG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITS R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAACCGACGACCCCCTGCTTGCAAAGCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupla amplifica&#231;&#227;o&#91;11&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GCCGCAAAGTTCTTTTCATG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ftsZ</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AGGTGAACGCGCTTGTATTTG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CAAAACGGTTGGAGAGCGT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CGCCTGTCATCTCATCAAGA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tempo real&#91;8&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CS F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ATGGGTTTTGGTCATCGAGT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">gltA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CS R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AAATCGACATTAGGGTAAAGTTTTT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3211273.png"
              ]
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Pr<span class="elsevierStyleItalic">imers</span> usados na investiga&#231;&#227;o molecular dos grupos de pacientes e controles</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
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        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Valores de p em <span class="elsevierStyleBold">negrito</span> nas tabelas s&#227;o estatisticamente significantes&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controle &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vasculopatia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&#8208;valor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade&#44; m&#233;dia</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DP</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#44;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#44;62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;001</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade&#44; mediana &#40;m&#237;n&#8208;m&#225;x&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;00 &#40;18&#44;0&#8208;51&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#44;50 &#40;15&#44;0&#8208;51&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;50 &#40;15&#44;0&#8208;51&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;39&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;29&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;68&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;048</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;27&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;31&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;66&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;33&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Contato com animais de cria&#231;&#227;o</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;10&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;19&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;29&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;007</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;55&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;14&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;70&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;66&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;34&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Contato com animais silvestres</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;8&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;8&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;286<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;58&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;33&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;91&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;66&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;33&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mordedura ou Arranhadura</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                            3 => "N&#46;Y&#46;S&#46; Valente"
                            4 => "V&#46; Aoki"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Livedoid vasculopathy&#58; review of pathogenesis&#44; clinical presentation&#44; diagnostic workup&#44; and treatment"
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                          "etal" => false
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Artigo original
Detecção do DNA de Bartonella henselae no sangue de pacientes com vasculopatia livedoide
Marina Rovani Drummonda,b,
Autor para correspondência
mrovani@unicamp.br

Autor para correspondência.
, Luciene Silva dos Santosa,b, Lais Bomediano Souzac, Gabriela Nero Mitsuushia, Maria Letícia Cintrad, Andrea Fernandes Eloy da Costa Françaa, Elemir Macedo de Souzaa, Paulo Eduardo Neves Ferreira Velhoa,b
a Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
b Laboratório de Pesquisa Aplicada em Dermatologia e Infecção por Bartonella, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
c Departamento de Medicina, Pontifícia Universidade Católica de Campinas, Campinas, SP, Brasil
d Departamento de Anatomia Patológica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
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com hist&#243;ria de contato com gatos e que apresentava les&#245;es ulceradas dos membros inferiores de dif&#237;cil controle havia 12 anos &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 e 2</a>&#41;&#46; O exame anatomopatol&#243;gico evidenciou hipodermite em atividade associada &#224; vasculite leucocitocl&#225;stica e presen&#231;a de trombos hialinos frequentes&#44; com necrose fibrinoide da parede de pequenos vasos&#46; Observou&#8208;se tamb&#233;m dep&#243;sito de mucina e de hemossiderina&#44; al&#233;m de prolifera&#231;&#227;o vascular &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; Exclu&#237;das outras doen&#231;as&#44; a paciente foi conduzida como VL prim&#225;ria e tratada&#44; ao longo dos anos&#44; com vasodilatadores&#44; antiagregantes plaquet&#225;rios&#44; corticosteroides e ciclos de antibi&#243;ticos &#40;metronidazol&#44; penicilina e ciprofloxacina&#41;&#44; com melhoras transit&#243;rias&#46; Considerada a forte epidemiologia de contato com gatos&#44; 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controle negativo de PCR e controle positivo de PCR &#8208; cepa 3715 de <span class="elsevierStyleItalic">B&#46; henselae</span> registrada na Se&#231;&#227;o de Cole&#231;&#227;o de Culturas do Instituto Adolfo Lutz&#41;&#46; Al&#233;m disso&#44; em cada rea&#231;&#227;o foram testadas dilui&#231;&#245;es de <span class="elsevierStyleItalic">B&#46; henselae</span> para determinar a sensibilidade e o limite de detec&#231;&#227;o de cada PCR&#46; Todos esses m&#233;todos j&#225; foram descritos anteriormente&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;11</span></a> Os <span class="elsevierStyleItalic">primers</span> utilizados na investiga&#231;&#227;o molecular dos pacientes e volunt&#225;rios est&#227;o descritos na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Os amplificados obtidos que apresentaram qualidade para o sequenciamento foram enviados para compara&#231;&#227;o de similaridade com material depositado previamente&#46; O fluxograma dos procedimentos realizados est&#225; apresentado na <a class="elsevierStyleCrossRef" href="#fig0020">figura 4</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0030" class="elsevierStylePara elsevierViewall">Participaram do estudo 16 pacientes com VL prim&#225;ria e 32 indiv&#237;duos sem queixas cl&#237;nicas&#46; Todos responderam a um question&#225;rio cujos dados s&#227;o apresentados na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; Pode&#8208;se observar que o grupo controle era mais jovem &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; com m&#233;dia et&#225;ria de 26&#44;71 anos&#59; j&#225; entre os pacientes&#44; a m&#233;dia foi de 37&#44;62 anos&#46; O grupo controle foi composto por mais homens que o grupo dos pacientes &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;048&#41;&#46; Os indiv&#237;duos do grupo controle tiveram mais contato com animais de cria&#231;&#227;o &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#44; foram mais mordidos e&#47;ou arranhados &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#41; e foram mais expostos a artr&#243;podes &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#41;&#46; N&#227;o houve diferen&#231;a significante &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05&#41; na compara&#231;&#227;o entre essas caracter&#237;sticas dentre aqueles que tiveram detec&#231;&#227;o do DNA de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; e os que n&#227;o tiveram&#44; em cada um dos grupos separadamente&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">O gene constitutivo &#40;GAPDH&#41; foi detectado em todas as amostras de pacientes e volunt&#225;rios&#44; garantindo a qualidade do DNA extra&#237;do para as an&#225;lises e a aus&#234;ncia de inibidores para as rea&#231;&#245;es moleculares&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Na PCR convencional para <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; o limite de detec&#231;&#227;o foi de 50 c&#243;pias&#44; e de 10 c&#243;pias na PCR <span class="elsevierStyleItalic">nested</span> e na PCR em tempo real&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O DNA de <span class="elsevierStyleItalic">B&#46; henselae</span> foi detectado em quatro pacientes em&#44; pelo menos&#44; uma rea&#231;&#227;o esp&#233;cie&#8208;espec&#237;fica&#46; No grupo controle&#44; o DNA foi detectado em quatro volunt&#225;rios&#46; Puderam ser sequenciados os amplificados de seis participantes dos oito com detec&#231;&#227;o do DNA bacteriano&#44; e todos os amplificados apresentaram 99&#37; a 100&#37; de similaridade com <span class="elsevierStyleItalic">B&#46; henselae</span> &#40;n&#250;mero de acesso GenBank&#58; CP020742&#46;1&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">N&#227;o foi observado crescimento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em cultura s&#243;lida de nenhuma amostra dos 48 participantes&#46; N&#227;o houve signific&#226;ncia estat&#237;stica pelo teste de Fischer na detec&#231;&#227;o do DNA da bact&#233;ria entre os dois grupos &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;413&#41;&#44; como tamb&#233;m observado na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Considerando que a VL prim&#225;ria &#233; manifesta&#231;&#227;o rara&#44; e utilizando o teste exato de Fisher para estabelecer o c&#225;lculo amostral do estudo e definindo o n&#237;vel de signific&#226;ncia em 5&#37; &#40;erro alfa ou tipo I&#41; com poder amostral de 80&#37; &#40;erro beta ou tipo II de 20&#37;&#41;&#44; com base nos dados obtidos&#44; pode&#8208;se estabelecer que a amostra m&#237;nima para que os resultados tenham signific&#226;ncia estat&#237;stica seria de 106 pacientes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0060" class="elsevierStylePara elsevierViewall">N&#227;o foi encontrado pelos autores nenhum trabalho na literatura relacionando infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; &#224; VL&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Da mesma maneira que foi proposto para o SARS&#8208;CoV&#8208;2&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> &#233; poss&#237;vel que a infec&#231;&#227;o persistente por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; tamb&#233;m cause dano vascular direto ou promova estado de hipercoagulabilidade&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Sabe&#8208;se que a VL &#233; uma doen&#231;a vaso&#8208;oclusiva com hialiniza&#231;&#227;o e trombose de vasos d&#233;rmicos&#59; muitos pacientes se queixam de dor e parestesia&#46; Todos os pacientes do estudo referiram dor intensa associada &#224; presen&#231;a de &#250;lceras&#44; e a maioria referiu parestesia ou dor leve ap&#243;s a cicatriza&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> H&#225; v&#225;rios artigos que relacionam dores cr&#244;nicas &#224; infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#8211;15</span></a> Estudos translacionais documentam hipersensibilidade dolorosa em camundongos infectados com <span class="elsevierStyleItalic">B&#46; henselae</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#44;17</span></a> Esses micro&#8208;organismos causam infec&#231;&#227;o intraendotelial e poderiam estimular a s&#237;nteses de endotelina &#40;ET&#8208;1&#41;&#44; um potente vasoconstritor&#44; que &#233; relacionado &#224; parestesia e dor&#44; incluindo dor cr&#244;nica&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#44;16&#44;18&#44;19</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Em tr&#234;s quartos dos pacientes n&#227;o foi poss&#237;vel detectar o DNA de <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; o que n&#227;o surpreende&#44; j&#225; que a VL &#233; uma manifesta&#231;&#227;o cut&#226;nea de diferentes enfermidades&#46; Al&#233;m disso&#44; <span class="elsevierStyleItalic">B&#46; henselae</span> causa bacteremia c&#237;clica&#44; e as amostras sangu&#237;neas podem ter sido obtidas nos intervalos em que a bact&#233;ria n&#227;o estava circulando&#46; Diferentes autores mostram que a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; tem maior chance de ser diagnosticada por bi&#243;psia de fragmentos teciduais em vez de amostra sangu&#237;nea&#44; e que os resultados dessa diferen&#231;a podem ser de maior import&#226;ncia e signific&#226;ncia estat&#237;stica&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#8211;23</span></a> Por quest&#245;es &#233;ticas&#44; foram coletadas apenas amostras sangu&#237;neas para minimizar os danos aos volunt&#225;rios do grupo controle&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; n&#227;o h&#225; m&#233;todo padr&#227;o ouro de diagn&#243;stico para infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; e resultados falso&#8208;negativos s&#227;o frequentes&#44; mesmo quando usada plataforma com t&#233;cnicas moleculares e microbiol&#243;gicas&#46; A necessidade de m&#250;ltiplos testes para detec&#231;&#227;o adequada desse micro&#8208;organismo visando reduzir falso&#8208;negativos j&#225; foi discutida por Drummond et al&#46; As t&#233;cnicas moleculares t&#234;m como limita&#231;&#227;o baixa sensibilidade &#40;m&#237;nimo de 4&#46;000 c&#243;pias&#47;mL no laborat&#243;rio onde foram realizadas as an&#225;lises&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Mesmo em doen&#231;as em que h&#225; o envolvimento tecidual&#44; a identifica&#231;&#227;o do agente no exame anatomopatol&#243;gico tem baixa sensibilidade&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Historicamente&#44; as colora&#231;&#245;es com impregna&#231;&#227;o de prata s&#227;o utilizadas para a detec&#231;&#227;o de esp&#233;cies de <span class="elsevierStyleItalic">Bartonella</span>&#59; no entanto&#44; como a colora&#231;&#227;o n&#227;o &#233; espec&#237;fica&#44; a leitura pode ser dif&#237;cil em decorr&#234;ncia da forma&#231;&#227;o de precipitado de prata&#46; Estudo de Caponetti et al&#46; avaliou o uso da imuno&#8208;histoqu&#237;mica &#40;IHQ&#41; para identifica&#231;&#227;o de <span class="elsevierStyleItalic">B&#46; henselae</span> na DAG em 24 casos de linfadenite&#44; a partir de bi&#243;psias fixadas em formalina e inclu&#237;dos em parafina&#44; e comparou os resultados com impregna&#231;&#227;o por prata &#40;IP&#41; e PCR&#46; Os casos positivos foram os seguintes&#58; IP&#44; 11 &#40;46&#37;&#41;&#59; PCR&#44; 9 &#40;38&#37;&#41;&#59; e IHQ&#44; 6 &#40;25&#37;&#41;&#46; Apenas dois casos &#40;8&#37;&#41; foram positivos para todos os tr&#234;s estudos&#46; A IP mostrou&#8208;se mais sens&#237;vel&#44; mas menos espec&#237;fica&#46; Apesar de 11 &#40;46&#37;&#41; dos casos do estudo terem sido positivos usando IP&#44; apenas seis dessas amostras foram concomitantemente positivas por an&#225;lise IHQ e&#47;ou PCR&#46; Esse achado sugere que v&#225;rios dos casos interpretados como positivos pela IP podem representar falso&#8208;positivos&#44; e que a sensibilidade diagn&#243;stica desses tr&#234;s testes &#233; baixa para DAG&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> Outro estudo com 106 casos de endocardite comparou os resultados de IHQ&#44; <span class="elsevierStyleItalic">Western blotting</span> e PCR em tempo real de sangue total&#44; soro e tecido valvar&#46; A IHQ e a colora&#231;&#227;o de Warthin&#8208;Starry foram as t&#233;cnicas menos sens&#237;veis&#46; Neste estudo&#44; a colora&#231;&#227;o de Warthin&#8208;Starry foi o mais sens&#237;vel desses dois m&#233;todos &#40;cinco amostras foram positivas para colora&#231;&#227;o de Warthin&#8208;Starry e negativas na an&#225;lise IHQ&#41;&#46; Entretanto&#44; esta colora&#231;&#227;o histol&#243;gica n&#227;o &#233; espec&#237;fica para <span class="elsevierStyleItalic">Bartonella</span> spp&#46; Como o processo infeccioso pode ser localizado&#44; um resultado imuno&#8208;histoqu&#237;mico negativo n&#227;o exclui definitivamente o diagn&#243;stico de endocardite por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> J&#225; o isolamento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; &#233; dif&#237;cil mesmo em condi&#231;&#245;es espec&#237;ficas e ideais&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">A bacteremia p&#244;de ser documentada no caso &#237;ndice&#44; pelo isolamento da bact&#233;ria em meio s&#243;lido mesmo ap&#243;s um ano de tratamento com doxiciclina&#44; mas n&#227;o houve isolamento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em nenhum dos participantes do estudo&#46; A dificuldade de tratar a infec&#231;&#227;o com antibi&#243;ticos&#44; como observado na febre das trincheiras &#40;causada por <span class="elsevierStyleItalic">Bartonella quintana</span>&#41; e na febre de Oroya &#40;que &#233; a primeira manifesta&#231;&#227;o da doen&#231;a bif&#225;sica da doen&#231;a de Carri&#243;n&#44; que pode evoluir para verruga peruana e &#233; causada por <span class="elsevierStyleItalic">Bartonella bacilliformis</span>&#41;&#44; sugerem que essas bact&#233;rias n&#227;o s&#227;o erradicadas&#46; Essa potencial persist&#234;ncia da infec&#231;&#227;o impossibilita garantir que manifesta&#231;&#245;es observadas na VL sejam rea&#231;&#245;es imunes infecciosas ou p&#243;s&#8208;infecciosas&#44; como se tem aventado&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Poucos grupos de pesquisa realizam cultura s&#243;lida para isolamento de <span class="elsevierStyleItalic">Bartonella</span> spp&#46; Isso porque o isolamento depende de meios espec&#237;ficos e incuba&#231;&#227;o prolongada&#46; Al&#233;m disso&#44; o crescimento fastidioso e a falta de sucesso no primo&#8208;isolamento fazem com que esse tipo de diagn&#243;stico n&#227;o seja vi&#225;vel&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Como a VL &#233; a express&#227;o cut&#226;nea de diferentes doen&#231;as&#44; a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; poderia ser apenas uma das causas dessa manifesta&#231;&#227;o&#46; Al&#233;m disso&#44; por infectar as c&#233;lulas endoteliais e ser o &#250;nico g&#234;nero conhecido de bact&#233;rias a estimular sua prolifera&#231;&#227;o em humanos&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> a pesquisa em amostras sangu&#237;neas pode n&#227;o representar a real condi&#231;&#227;o do paciente em rela&#231;&#227;o &#224; infec&#231;&#227;o por essas bact&#233;rias&#44; pois a bacteremia costuma ser c&#237;clica&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Dados coletados no question&#225;rio de fatores de risco para bartonelose &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41; mostraram que os volunt&#225;rios do grupo controle eram significantemente mais jovens&#44; uma vez que a maioria desses volunt&#225;rios &#233; composta por estudantes da Unicamp&#46; A VL acomete mais mulheres&#44; e houve diferen&#231;a estat&#237;stica entre a propor&#231;&#227;o dos sexos dos grupos&#46; Uma limita&#231;&#227;o do estudo &#233; que os volunt&#225;rios eram mais expostos a fatores de risco para adquirir a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; fatores esses observados em estudo realizado com doadores de sangue do Hemocentro da Unicamp&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> uma vez que relataram&#44; em maior n&#250;mero em rela&#231;&#227;o aos pacientes&#44; terem sofrido mordidas e arranhaduras&#44; contato com animais de cria&#231;&#227;o e exposi&#231;&#227;o a artr&#243;podes&#46; Mesmo com menor exposi&#231;&#227;o de risco&#44; o grupo de pacientes com VL apresentou o dobro da taxa de infec&#231;&#227;o &#40;25&#37;&#59; 4&#47;16&#41;&#44; o que pode indicar que a preval&#234;ncia da infec&#231;&#227;o por <span class="elsevierStyleItalic">B&#46; henselae</span> nos pacientes seja maior e que essas bact&#233;rias possam&#44; de fato&#44; ter rela&#231;&#227;o com o desencadeamento da doen&#231;a&#46; Outra justificativa para n&#227;o ter sido encontrada diferen&#231;a estat&#237;stica &#233; o pequeno n&#250;mero de pacientes do estudo&#44; que avalia pacientes com doen&#231;a rara e que foi realizado como piloto em uma &#250;nica institui&#231;&#227;o&#46; Como descrito nos resultados&#44; usando como controle volunt&#225;rios com as mesmas caracter&#237;sticas&#44; seria necess&#225;rio um n&#250;mero de pacientes quase sete vezes maior para documentar a signific&#226;ncia estat&#237;stica&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A inexist&#234;ncia de padr&#227;o ouro&#44; aliada &#224; grande dificuldade em se detectar a bacteremia causada por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;&#44; refor&#231;am a necessidade de se utilizar m&#233;todos diversos e complementares visando aumentar a sensibilidade e a precis&#227;o do diagn&#243;stico&#46; Essa combina&#231;&#227;o de m&#233;todos e de testagem de diferentes amostras torna o diagn&#243;stico laboratorial mais eficaz e tem sido utilizada por diferentes grupos de pesquisa&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;20&#44;28&#8211;30</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0110" class="elsevierStylePara elsevierViewall">O DNA de <span class="elsevierStyleItalic">B&#46; henselae</span> foi detectado em um de cada quatro pacientes com VL prim&#225;ria&#44; o que refor&#231;a a necessidade de investigar a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; nesses indiv&#237;duos&#44; ainda que n&#227;o tenha havido diferen&#231;a estat&#237;stica entre o grupo de pacientes e o grupo controle&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0115" class="elsevierStylePara elsevierViewall">Bolsa de Doutorado CNPq 170501&#47;2018&#8208;3 &#40;Santos&#44; LS&#41;&#59; bolsa de P&#243;s&#8208;Doutorado Fapesp 2018&#47;12565&#8208;6 &#40;Drummond&#44; MR&#41;&#59; bolsa produtividade CNPq 301900&#47;2015&#8208;9 &#40;Velho&#44; PENF&#41;&#59; Fundo de Apoio &#224; Dermatologia de S&#227;o Paulo &#40;Funadersp&#41;&#47;Sociedade Brasileira de Dermatologia&#44; Regional S&#227;o Paulo &#40;Fran&#231;a&#44; AFEC&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0120" class="elsevierStylePara elsevierViewall">Marina Rovani Drummond&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Luciene Silva dos Santos&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Lais Bomediano Souza&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Gabriela Nero Mitsuushi&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; participa&#231;&#227;o sele&#231;&#227;o dos pacientes e coleta das amostras&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Maria Let&#237;cia Cintra&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Andrea Fernandes Eloy da Costa Fran&#231;a&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Elemir Macedo de Souza&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Paulo Eduardo Neves Ferreira Velho&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o sele&#231;&#227;o dos pacientes e coleta das amostras&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflito de interesses</span><p id="par0160" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A vasculopatia livedoide &#40;VL&#41; manifesta&#8208;se como &#250;lceras e cicatrizes atr&#243;ficas nacaradas nas extremidades inferiores&#46; O principal fator etiopatog&#234;nico &#233; a hipercoagulabilidade&#44; com a forma&#231;&#227;o de trombos seguida de inflama&#231;&#227;o&#46; Trombofilia&#44; doen&#231;as do col&#225;geno e doen&#231;as mieloproliferativas podem levar &#224; VL&#44; mas a forma idiop&#225;tica &#40;prim&#225;ria&#41; predomina&#46; <span class="elsevierStyleItalic">Bartonella</span> spp&#46; podem causar infec&#231;&#227;o intraendotelial&#59; as manifesta&#231;&#245;es cut&#226;neas da infec&#231;&#227;o por essas bact&#233;rias podem ser diversas&#44; incluindo vasculite leucocitocl&#225;stica e &#250;lceras&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A partir de um caso cl&#237;nico&#44; o objetivo deste estudo foi investigar a bacteremia por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em pacientes com &#250;lceras cr&#244;nicas de dif&#237;cil controle diagnosticadas como VL prim&#225;ria&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram aplicados question&#225;rios e realizados testes moleculares &#40;PCR convencional&#44; PCR de dupla amplifica&#231;&#227;o e PCR em tempo real&#41;&#44; culturas l&#237;quidas e s&#243;lidas em amostras sangu&#237;neas e <span class="elsevierStyleItalic">pellets</span> de c&#233;lulas de 16 pacientes com VL prim&#225;ria e 32 volunt&#225;rios saud&#225;veis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O DNA de <span class="elsevierStyleItalic">Bartonella henselae</span> foi detectado em 25&#37; dos pacientes com VL e em 12&#44;5&#37; dos indiv&#237;duos do grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;413&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Pela raridade da VL prim&#225;ria&#44; o n&#250;mero de pacientes estudados foi pequeno e houve maior exposi&#231;&#227;o do grupo controle a fatores de risco para infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Embora sem diferen&#231;a estat&#237;stica significante entre os grupos&#44; o DNA de <span class="elsevierStyleItalic">B&#46; henselae</span> foi detectado em um de cada quatro pacientes&#44; o que refor&#231;a a necessidade de investigar a infec&#231;&#227;o por <span class="elsevierStyleItalic">Bartonella</span> spp&#46; em pacientes com VL prim&#225;ria&#46;</p></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sequ&#234;ncia de nucleot&#237;deos &#40;5&#8217;&#8208;3&#8217;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alvo molecular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Convencional&#91;9&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAPDH F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCTTCATTGACCTCAACTACAT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAPDH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAPDH R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCAAACTTGTCATGGATGACC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Convencional&#91;10&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITS F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CTTCAGATGATGATCCCAAGCCTTYTGGCG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITS R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAACCGACGACCCCCTGCTTGCAAAGCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupla amplifica&#231;&#227;o&#91;11&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GCCGCAAAGTTCTTTTCATG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ftsZ</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AGGTGAACGCGCTTGTATTTG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CAAAACGGTTGGAGAGCGT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BH A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CGCCTGTCATCTCATCAAGA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tempo real&#91;8&#93;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CS F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ATGGGTTTTGGTCATCGAGT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">gltA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CS R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AAATCGACATTAGGGTAAAGTTTTT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controle &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vasculopatia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&#8208;valor&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Idade&#44; m&#233;dia</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DP</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">37&#44;62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;001</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Idade&#44; mediana &#40;m&#237;n&#8208;m&#225;x&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;00 &#40;18&#44;0&#8208;51&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#44;50 &#40;15&#44;0&#8208;51&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;50 &#40;15&#44;0&#8208;51&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19 &#40;39&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;29&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;68&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;048</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;27&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;31&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Contato com animais de cria&#231;&#227;o</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;55&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;14&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;70&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31 &#40;66&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Contato com animais silvestres</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;286<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44 &#40;91&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;66&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mordedura ou Arranhadura</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;000</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;14&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;27&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ausente&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;66&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;33&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Exposi&#231;&#227;o a artr&#243;podes</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">29 &#40;60&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;16&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;003</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;6&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;66&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Detec&#231;&#227;o do DNA de Bartonella henselae</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;8&#44;35&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">8 &#40;16&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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ISSN: 26662752
Idioma original: Português
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