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CLINICAL SCIENCE
Intestinal microsporidiosis: a hidden risk in rheumatic disease patients undergoing anti-tumor necrosis factor therapy combined with disease-modifying anti-rheumatic drugs?
Nadia Emi AikawaI,II,
Corresponding author
nadia.aikawa@gmail.com

Tel.: 005511-3069-8563, Fax: 005511-3069-8503
, Aline de Oliveira TwardowskyII, Jozélio Freire de CarvalhoI, Clovis A SilvaI,II, Ivan Leonardo Avelino França e SilvaIII, Ana Cristina de Medeiros RibeiroI, Carla Gonçalves Schain SaadI, Julio César Bertacini MoraesI, Roberto Acayaba de ToledoIV, Eloísa BonfáI
I Division of Rheumatology, CEDMAC Unit, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP/Brazil.
II Pediatric Reumatology Unit, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP/Brazil.
III Division of Infectology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP/Brazil.
IV Division of Rheumatology, CEDMAC Unit, Faculdade de Medicina de São José do Rio Preto, SP/Brazil.
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Microsporidia has emerged in recent years as an opportunistic infectious agent with a ubiquitous distribution&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#8211;4</a> The clinical manifestations of this infection vary widely&#44; from none &#40;asymptomatic&#41; to non-bloody watery diarrhea&#44; abdominal cramps&#44; weight loss&#44; and disseminated disease&#44; especially in immunosuppressed subjects&#46;<a class="elsevierStyleCrossRefs" href="#bib2">2&#8211;4</a></p><p id="para20" class="elsevierStylePara elsevierViewall">This parasitological disease primarily affects immunosuppressed patients&#44;<a class="elsevierStyleCrossRefs" href="#bib1">1&#8211;4</a> particularly those with human immunodeficiency virus &#40;HIV&#41;&#44; malignancies and diabetes mellitus&#44; as well as patients post heart-lung&#44; liver&#44; and renal transplantations&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;2</a> In addition&#44; this infection also occurs in patients undergoing immunosuppressive drug treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib2">2&#44;4</a></p><p id="para30" class="elsevierStylePara elsevierViewall">In fact&#44; patients with rheumatic diseases who are taking disease-modifying anti-rheumatic drugs &#40;DMARD&#41; and anti-tumor necrosis factor &#40;TNF&#41; therapy have a high risk for general infections&#44;<a class="elsevierStyleCrossRefs" href="#bib5">5&#8211;7</a> including intestinal pathogenic parasite infestations such as <span class="elsevierStyleItalic">Strongyloides stercoralis</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib8">8&#44;9</a> However&#44; to our knowledge&#44; there are no data regarding the risk of microsporidiosis in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#8211;13</a></p><p id="para40" class="elsevierStylePara elsevierViewall">Therefore&#44; the objective of this study was to evaluate the frequency and clinical significance of microsporidiosis in patients with rheumatic diseases who are undergoing anti-TNF&#47;DMARD treatment compared to an age- and socio-economic condition-matched healthy population&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIALS AND METHODS</span><p id="para50" class="elsevierStylePara elsevierViewall">We evaluated 89 consecutive patients at our hospital who were diagnosed with rheumatoid arthritis &#40;RA&#41; &#40;American College of Rheumatology criteria&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib14">14</a> ankylosing spondylitis &#40;AS&#41; &#40;New York criteria&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib15">15</a> or psoriatic arthritis &#40;PsA&#41; &#40;European spondyloarthropathy Study Group &#8211; ESSG criteria and Moll and Wright classification&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib16">16</a> All patients were undergoing anti-TNF therapy &#40;adalimumab&#44; etanercept&#44; or infliximab&#41; combined with DMARDs&#46; The control group included 92 healthy employees of our hospital who were matched by age and socio-economic status&#46; Prior to this study&#44; no specific routine existed in our Infusion Center with regard to stool examination for parasites and fecal leukocytes before anti-TNF therapy&#46; The prophylactic use of anti-helminthic drugs was recommended for patients under concomitant glucocorticoid therapy&#46;</p><p id="para60" class="elsevierStylePara elsevierViewall">This study was approved by the local ethics committee&#44; and informed consent was obtained from each participant or his or her legal guardian&#46;</p><p id="para70" class="elsevierStylePara elsevierViewall">Demographic data&#44; the number of school years attended&#44; and the socio-economic status &#40;according to <span class="elsevierStyleItalic">Associa&#231;&#227;o Brasileira dos Institutos de Pesquisa de Mercados</span>&#41;<a class="elsevierStyleCrossRef" href="#bib17">17</a> were recorded&#46; Background information and parasitosis symptoms in patients and control participants were acquired via interview and included the following&#58; general &#40;loss of appetite&#44; weight loss&#44; and adynamia&#41;&#44; gastrointestinal &#40;abdominal pain&#44; abdominal distension&#44; flatulence&#44; diarrhea&#44; dysentery&#44; tenesmus&#44; obstipation&#44; nausea&#44; vomiting&#44; hematochezia&#44; and worm elimination&#41;&#44; cutaneous &#40;exanthema&#41;&#44; and pulmonary manifestations &#40;wheezing&#44; thoracic pain&#44; and hemoptysis&#41;&#46;</p><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Disease activity and laboratory evaluation of rheumatic diseases</span><p id="para80" class="elsevierStylePara elsevierViewall">Disease activity was evaluated by the following&#58; the duration of morning stiffness&#44; the number of swollen and&#47;or painful joints&#44; and the disease activity score &#40;DAS28&#41; for RA patients<a class="elsevierStyleCrossRef" href="#bib18">18</a> and the number of swollen and&#47;or painful joints and the Bath Ankylosing Spondylitis Disease Activity Index &#40;BASDAI&#41;<a class="elsevierStyleCrossRef" href="#bib19">19</a> for AS and PsA patients&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">The laboratory parameters assessed included the erythrocyte sedimentation rate &#40;ESR&#41; according to Westergreen &#40;mm&#47;<span class="elsevierStyleSup">1st</span> hour&#41; and C-reactive protein &#40;CRP&#41; level determined by nephelometry &#40;mg&#47;L&#41;&#46; Data concerning current treatment with prednisone&#44; DMARDs&#44; anti-TNF and immunosuppressive drugs &#40;methotrexate&#44; azathioprine&#44; leflunomide&#44; chloroquine&#44; sulfasalazine and&#47;or cyclosporine&#41; were collected&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Parasitological assessment</span><p id="para100" class="elsevierStylePara elsevierViewall">Three stool samples were collected from rheumatic disease patients and control subjects on different days and placed into plastic vials without preservatives&#46; The stool samples were microscopically analyzed for the detection of protozoan oocysts&#44; cysts&#44; helminth eggs&#44; and larvae by a qualified technician blinded to the groups using the techniques described by Faust et al&#44; Rugai and Lutz &#40;modified&#41;&#44; and Hoffman&#44; Pons and Janer&#46;<a class="elsevierStyleCrossRef" href="#bib20">20</a></p><p id="para110" class="elsevierStylePara elsevierViewall">Microsporidia positivity was defined as the isolation of at least one parasite using the GRAM-Chromotrope<a class="elsevierStyleCrossRef" href="#bib21">21</a> technique&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">Intestinal coccidia were evaluated by the GRAM-Chromotrope<a class="elsevierStyleCrossRef" href="#bib21">21</a> technique&#59; Leishman staining<a class="elsevierStyleCrossRef" href="#bib22">22</a> was used to identify <span class="elsevierStyleItalic">Blastocystis hominis</span> and fecal leukocytes&#59; the Kinyoun procedure<a class="elsevierStyleCrossRef" href="#bib23">23</a> and capture enzyme-linked immunosorbent assay &#40;capture ELISA&#41; were used to detect <span class="elsevierStyleItalic">Cryptosporidium sp</span>&#46;&#44; <span class="elsevierStyleItalic">Cyclospora cayetanensis&#44;</span> and <span class="elsevierStyleItalic">Isospora belli&#59;</span> and Kato-Katz was used to detect <span class="elsevierStyleItalic">Schistosoma mansoni</span>&#46;<a class="elsevierStyleCrossRef" href="#bib24">24</a> Coproculture was also performed using SS agar&#44; MacConkey agar or Karmali plate agar&#46;<a class="elsevierStyleCrossRef" href="#bib25">25</a></p><p id="para130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Giardia lamblia&#44; Strongyloides stercoralis&#44; Ancilostoma duodenali&#44; Ascaris lumbricoides&#44; Entamoeba histolytica&#44; Microsporidia</span> &#40;positive stool leukocytes&#41;&#44; <span class="elsevierStyleItalic">Entamoeba dispar&#44; Dientamoeba fragilis&#44; Cryptosporidium parvum&#44; Cyclospora cayetanensis&#44; Isospora belli&#44;</span> and <span class="elsevierStyleItalic">Blastocystis hominis</span> &#40;positive stool leukocytes&#41; were defined as pathogenic parasites in immunocompromised patients&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a> All participants with positive pathogenic parasites were treated with the appropriate recommended antiparasitic drugs&#46;<a class="elsevierStyleCrossRef" href="#bib26">26</a></p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Statistical analysis</span><p id="para140" class="elsevierStylePara elsevierViewall">Results are presented as the mean &#177; standard deviation or the median &#40;range&#41; for continuous variables and the number &#40;&#37;&#41; for categorical variables&#46; Continuous variables were compared using the <span class="elsevierStyleItalic">t</span> test and the Mann Whitney test to evaluate differences between patients with and without intestinal microsporidia and other parasitoses&#46; For categorical variables&#44; differences in proportions were assessed by Fisher&#39;s exact test&#46; For all statistical tests&#44; significance was set at a <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#46;</p></span></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">RESULTS</span><p id="para150" class="elsevierStylePara elsevierViewall">A total of 89 patients with rheumatic diseases &#40;47 RA&#44; 31 AS and 11 PsA&#41; and 92 healthy control subjects were included in this study&#46; The two groups were comparable with regard to the mean current age &#40;47&#46;2&#177;10&#46;9 <span class="elsevierStyleItalic">vs&#46;</span> 43&#46;8&#177;14&#46;3 years&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;094&#41;&#44; percentage who were Caucasian &#40;80 <span class="elsevierStyleItalic">vs&#46;</span> 73&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;3&#41; and socio-economic distribution&#44; with a similar predominance of the middle and lowest Brazilian socio-economic classes &#40;C&#44; D or E&#41;<a class="elsevierStyleCrossRef" href="#bib17">17</a> based on scholarity and ownership of household items &#40;84 <span class="elsevierStyleItalic">vs&#46;</span> 82&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;7&#41;&#46; There were a greater proportion of females in the control group than in the patient group &#40;93 <span class="elsevierStyleItalic">vs&#46;</span> 62&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#46; The mean disease duration for all patients was 15&#46;5&#177;8&#46;6 years&#46;</p><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Intestinal parasites</span><p id="para160" class="elsevierStylePara elsevierViewall">The overall frequency of pathogenic parasites was similar in both the patient and control groups &#40;63 <span class="elsevierStyleItalic">vs&#46;</span> 58&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;54&#41;&#46; Positive tests for microsporidia were significantly higher in all types of rheumatic disease patients compared with the control subjects &#40;38 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#44; and microsporidia plus positive fecal leukocytes were also more frequently detected in patients than in control subjects &#40;31 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#46; Of note&#44; 81&#46;6&#37; of the positive microsporidia patients had concomitant fecal leukocytes&#46; In contrast&#44; no differences were detected for other pathogenic parasites &#40;<span class="elsevierStyleItalic">Entamoeba histolytica&#47;dispar&#44; Dientamoeba fragilis&#44; Giardia lamblia&#44; Cryptosporidium parvum&#44; Cyclospora cayetanensis&#44; Isospora belli&#44; Ancilostoma duodenale&#44; Ascaris lumbricoides&#44;</span> and <span class="elsevierStyleItalic">Blastocystis hominis</span> with leukocytes&#41; and non-pathogenic parasites &#40;<span class="elsevierStyleItalic">Endolimax nana&#44; Entamoeba coli&#44;</span> and <span class="elsevierStyleItalic">Entamoeba hartmanni</span>&#41; &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#59; <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#41;&#46; Among the 28 patients with microsporidia and positive stool leukocytes&#44; 36&#37; had other concomitant pathogenic parasites&#44; particularly <span class="elsevierStyleItalic">Blastocystis hominis</span> &#91;8&#47;28 &#40;29&#37;&#41; patients&#93;&#59; however&#44; no association of microsporidia and <span class="elsevierStyleItalic">Blatocystis hominis</span> was observed &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;28&#41;&#46; Regarding the prevalence of pathogenic parasites in each disease compared to the control group&#44; microsporidiosis was higher in RA &#40;32 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#44; AS &#40;45 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41; and PsA patients &#40;40 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#46; Moreover&#44; there were no statistical differences in microsporidia positivity between the specific diseases &#40;RA <span class="elsevierStyleItalic">vs&#46;</span> AS and PsA&#59; AS <span class="elsevierStyleItalic">vs&#46;</span> PsA&#59; all <span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46; <span class="elsevierStyleItalic">Giardia lamblia</span> was significantly more common in AS patients <span class="elsevierStyleItalic">vs&#46;</span> control subjects &#40;10&#37; <span class="elsevierStyleItalic">vs&#46;</span> 0&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0149&#41;&#44; whereas no differences were observed for the other pathogenic parasites &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p id="para170" class="elsevierStylePara elsevierViewall">Disease activity parameters at the study onset were alike in patients with and without microsporidia infections for all diseases &#40;RA&#44; AS&#44; and PsA&#41; &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46; The analysis of the duration of anti-TNF&#47;DMARD therapy showed no statistical difference between patients with and without microsporidia infection &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;55&#41;&#46; The frequencies of glucocorticoid use in patients with and without microsporidiosis &#91;44&#37; &#40;95&#37; IC 0&#46;27-0&#46;62&#41; <span class="elsevierStyleItalic">vs&#46;</span> 64&#37; &#40;95&#37; IC 0&#46;49-0&#46;76&#41;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;08&#93; were alike&#44; as was the number of DMARDs used &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para180" class="elsevierStylePara elsevierViewall">No differences were detected in the frequencies of other infections that required antibiotic therapy in patients with and without microsporidiosis&#44; such as acute lower respiratory infection &#40;2&#46;9 <span class="elsevierStyleItalic">vs&#46;</span> 14&#46;5&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;14&#41;&#44; urinary tract infection &#40;29&#46;4 <span class="elsevierStyleItalic">vs&#46;</span> 30&#46;9&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 1&#46;0&#41; cutaneous infection &#40;20&#46;6 <span class="elsevierStyleItalic">vs&#46;</span> 23&#46;6&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;8&#41; and tuberculosis &#40;2&#46;9 <span class="elsevierStyleItalic">vs&#46;</span> 1&#46;8&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span> &#61; 1&#46;0&#41;&#46;</p><p id="para190" class="elsevierStylePara elsevierViewall">The comparison of rheumatic disease patients with and without microsporidiosis revealed that 85&#46;4&#37; of the patients had gastrointestinal symptoms such as diarrhea &#40;19&#37;&#41;&#44; abdominal pain &#40;22&#37;&#41;&#44; and weight loss &#40;11&#37;&#41;&#44; but these symptoms occurred just as frequently in patients with and without this infection &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46; Other signs and symptoms related to parasitoses were also comparable in the two groups&#44; with the exception of abdominal distension &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;013&#41; and adynamia &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;009&#41;&#44; both of which occurred less often in patients with microsporidiosis &#40;<a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a>&#41;&#46; No patient or control group had a disseminated infection&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia></span></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">DISCUSSION</span><p id="para200" class="elsevierStylePara elsevierViewall">This study is the first to identify a high frequency of microsporidia infections associated with intestinal mucosa disruption in rheumatic disease patients undergoing anti-TNF and DMARD therapies&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">The study design has several advantages&#44; including the inclusion of patients with well-established rheumatic disease criteria&#46;<a class="elsevierStyleCrossRefs" href="#bib14">14&#8211;16</a> In addition&#44; the Gram-Chromotrope stain methodology applied in this study is considered to be one of the most specific detection techniques with the best sensitivity for detecting microsporidia in fluids&#44; including feces&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a> Moreover&#44; external factors such as socio-economic conditions may influence parasitosis prevalence&#46; For example&#44; the frequency of microsporidia in HIV-infected patients was higher in Venezuela &#40;13&#46;6&#37;&#41;&#44; an underdeveloped country&#44; than in Italy &#40;1&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib27">27&#8211;28</a> This potential bias was greatly reduced by the matching of our patients with a control group with the same socio-financial distribution&#46; One limitation of our study was the absence of a control group of rheumatic disease patients treated only with DMARDs&#44; due to the impossibility of achieving an adequate matching for disease duration and severity in these patients&#46; In fact&#44; anti-TNF therapy is now being indicated very early for patients with these diseases&#46; There are&#44; however&#44; no data on the frequency of microsporidia infection in rheumatic disease patients without anti-TNF therapy&#46;</p><p id="para220" class="elsevierStylePara elsevierViewall">Microsporidia has emerged as an important cause of infectious complications in severely immunocompromised patients with HIV&#44; recipients of solid organ transplant and patients with hematological malignancies&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#8211;3</a> Cell-mediated immunity appears to be critical for protection against microsporidia through the T helper cell 1 &#40;Th1&#41; cytokine response&#46;<a class="elsevierStyleCrossRef" href="#bib3">3</a> The importance of a Th1 response in the resistance to microsporidial infection has been demonstrated by <span class="elsevierStyleItalic">in vitro</span> studies showing that knockout animals for Th1 cytokines such as interferon and interleukin-12 could not clear microsporidia infections&#46;<a class="elsevierStyleCrossRef" href="#bib29">29</a> In fact&#44; more severe microsporidia infections were observed in HIV-infected patients with declining CD4&#43; and CD8&#43; T-cell numbers&#46;<a class="elsevierStyleCrossRef" href="#bib29">29</a> Accordingly&#44; the inhibition of TNF-alpha&#44; a cytokine well known to be related to the Th1 response&#44;<a class="elsevierStyleCrossRef" href="#bib30">30</a> could possibly facilitate the microsporidia infestation observed in the present study&#46; Moreover&#44; experimental studies have reported a decrease in the specific protective IgG against microsporidia in animals treated with immunosuppressive drugs&#46;<a class="elsevierStyleCrossRef" href="#bib31">31</a> We have confirmed that microsporidia infestation is more prevalent in immunosuppressed patients<a class="elsevierStyleCrossRefs" href="#bib1">1&#8211;4</a> and have now extended this observation to rheumatic disease patients undergoing anti-TNF&#47;DMARD treatment&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">Microsporidiosis and intestinal parasitosis may present with diverse clinical manifestations&#44; depending on the host immune status and the microsporidium species&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#8211;4</a> Diarrhea and wasting syndromes are the most common complaints&#59;<a class="elsevierStyleCrossRefs" href="#bib1">1&#8211;4</a> however&#44; these parasite infections can be asymptomatic&#46; In fact&#44; the parasitosis in our study was frequently associated with gastrointestinal manifestations and concomitant stool leukocytes&#44; indicating a possible intestinal mucosa disruption&#44;<a class="elsevierStyleCrossRef" href="#bib32">32</a> which is a known risk for intestinal dissemination&#46;<a class="elsevierStyleCrossRef" href="#bib33">33</a></p><p id="para240" class="elsevierStylePara elsevierViewall">Infection is a major co-morbidity in rheumatic conditions&#44; and therapies such as conventional DMARDs and anti-TNF are known to enhance the risk of infection&#46;<a class="elsevierStyleCrossRefs" href="#bib34">34&#44;35</a> In this regard&#44; previous reports have suggested that susceptibility to infection may be distinct in different underlying rheumatic diseases&#46; The main explanation for this finding seems to be a disease-associated genetic background and immunosuppressive therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib36">36&#44;37</a> However&#44; in the present study&#44; no difference was observed in microsporidiosis frequency between the specific rheumatic diseases&#44; suggesting that anti-TNF&#47;DMARD treatment is a more relevant risk factor for this infestation than is the specific rheumatic disease itself&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">We have identified microsporidiosis to be a frequent infection that is associated with mucosal lesions in patients undergoing concomitant anti-TNF&#47;DMARD treatment&#46; This finding supports the notion that the recommendation for the prophylactic use of anti-helminthic drugs in patients on glucocorticoid therapy could be extended to those initiating anti-TNF therapy&#46;</p></span></span>"
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          "titulo" => "INTRODUCTION"
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          "titulo" => "MATERIALS AND METHODS"
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              "identificador" => "cesec30"
              "titulo" => "Disease activity and laboratory evaluation of rheumatic diseases"
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            1 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Parasitological assessment"
            ]
            2 => array:2 [
              "identificador" => "cesec50"
              "titulo" => "Statistical analysis"
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          ]
        ]
        3 => array:3 [
          "identificador" => "cesec60"
          "titulo" => "RESULTS"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Intestinal parasites"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "cesec80"
          "titulo" => "DISCUSSION"
        ]
        5 => array:1 [
          "titulo" => "REFERENCES"
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2011-01-12"
    "fechaAceptado" => "2011-03-21"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Microsporidia"
            1 => "Parasitosis"
            2 => "Anti-TNF"
            3 => "Rheumatoid arthritis"
            4 => "Ankylosing spondylitis"
          ]
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      ]
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    "resumen" => array:1 [
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE&#58;</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Immunosuppressed patients are at risk of microsporidiosis&#44; and this parasitosis has an increased rate of dissemination in this population&#46; Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor&#47;disease-modifying anti-rheumatic drug treatment&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Ninety-eight patients &#40;47 with rheumatoid arthritis&#44; 31 with ankylosing spondylitis and 11 with psoriatic arthritis&#41; and 92 healthy control patients were enrolled in the study&#46; Three stool samples and cultures were collected from each subject&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects &#40;36 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#44; as well as in those with rheumatic diseases &#40;32 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#44; ankylosing spondylitis &#40;45 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41; and psoriatic arthritis &#40;40 <span class="elsevierStyleItalic">vs&#46;</span> 4&#37;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;0001&#41;&#44; despite a similar social-economic class distribution in both the patient and control groups &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;1153&#41;&#46; Of note&#44; concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients &#40;79&#46;5&#37;&#41;&#46; Approximately 80&#37; of the patients had gastrointestinal symptoms&#44; such as diarrhea &#40;26&#37;&#41;&#44; abdominal pain &#40;31&#37;&#41; and weight loss &#40;5&#37;&#41;&#44; although the frequencies of these symptoms were comparable in patients with and without this infection &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46; Rheumatoid arthritis&#44; ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41;&#46; The duration of anti-tumor necrosis factor&#47;disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION&#58;</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor&#47;disease-modifying anti-rheumatic drug therapy&#46; Impaired host defenses due to the combination of the underlying disease and the immunosuppressive therapy is the most likely explanation for this finding&#44; and this increased susceptibility reinforces the need for the investigation of microsporidia and implementation of treatment strategies in this population&#46;</p></span>"
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            "titulo" => "METHODS&#58;"
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            "titulo" => "RESULTS&#58;"
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            "titulo" => "CONCLUSION&#58;"
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        "nota" => "<p class="elsevierStyleNotepara" id="cenpara10"><span class="elsevierStyleBold">Competing interest&#58;</span></p> <p class="elsevierStyleNotepara" id="cenpara20">This study was supported by grants from FAPESP &#40;2009&#47;51897-5 to EB&#41;&#44; CNPQ &#40;3300665&#47;2009-1 to JFC&#44; 300248&#47;2008-3 to CAS and 301411&#47;2009-3 to EB&#41;&#44; Federico Foundation &#40;to JFC&#44; CAS and EB&#41; and Wyeth &#40;to NEA&#41;&#46;</p>"
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          "leyenda" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Results are presented as n &#40;&#37;&#41;&#59; DMARDs - disease-modifying anti-rheumatic drugs&#46;</p>"
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                  \t\t\t\t  " align="left" valign="top" scope="col">Intestinal parasites&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top" scope="col">Rheumatic disease patients &#40;n &#61; 89&#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="center" valign="top" scope="col">Control subjects &#40;n &#61; 92&#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="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">Pathogenic parasites</span>&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">&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \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
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                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Microsporidia&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="center" valign="top">34 &#40;38&#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="center" valign="top">4 &#40;4&#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  " align="char" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top">28 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4 &#40;4&#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="char" valign="top">&#60;0&#46;0001&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Entamoeba histolytica&#47;dispar</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="center" valign="top">0 &#40;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="center" valign="top">4 &#40;4&#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="char" valign="top">0&#46;12&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dientamoeba fragilis</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="center" valign="top">3 &#40;3&#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="center" valign="top">0 &#40;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="char" valign="top">0&#46;12&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Giardia lamblia</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="center" valign="top">3 &#40;3&#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="center" valign="top">0 &#40;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="char" valign="top">0&#46;12&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Strongyloides stercoralis</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="center" valign="top">3 &#40;3&#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="center" valign="top">2 &#40;2&#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="char" valign="top">0&#46;68&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cryptosporidium parvum</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="center" valign="top">3 &#40;3&#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="center" valign="top">5 &#40;5&#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="char" valign="top">0&#46;72&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cyclospora cayetanensis</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="center" valign="top">0 &#40;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="center" valign="top">0 &#40;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="char" valign="top">1&#46;0&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Isospora belli</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="center" valign="top">0 &#40;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="center" valign="top">0 &#40;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="char" valign="top">1&#46;0&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ancilostoma duodenale</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="center" valign="top">1 &#40;1&#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="center" valign="top">0 &#40;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="char" valign="top">0&#46;49&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ascaris lumbricoides</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="center" valign="top">0 &#40;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="center" valign="top">0 &#40;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="char" valign="top">1&#46;0&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Blastocystis hominis</span> with leukocytes&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="center" valign="top">46 &#40;52&#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="center" valign="top">42 &#40;46&#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="char" valign="top">0&#46;46&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="top"><span class="elsevierStyleBold">Non-pathogenic parasites</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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Endolimax nana</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="center" valign="top">17 &#40;19&#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="center" valign="top">25 &#40;27&#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="char" valign="top">0&#46;22&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="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Entamoeba coli</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="center" valign="top">6 &#40;7&#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="center" valign="top">12 &#40;13&#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="char" valign="top">0&#46;21&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="top" style="border-bottom: 2px solid black"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Entamoeba hartmanni</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="center" valign="top" style="border-bottom: 2px solid black">1 &#40;1&#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="center" valign="top" style="border-bottom: 2px solid black">1 &#40;1&#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="char" valign="top" style="border-bottom: 2px solid black">0&#46;5&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">Parameters&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Patients with microsporidia &#40;n &#61; 34&#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="center" valign="top" scope="col">Patients without microsporidia &#40;n &#61; 55&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">Rheumatoid arthritis &#40;n &#61; 47&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Morning stiffness&#44; minutes&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="center" valign="top">13&#177;17&#46;9&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="center" valign="top">26&#46;9&#177;43&#46;2&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="center" valign="top">0&#46;24&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of painful joints&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="center" valign="top">6&#46;5&#177;5&#46;8&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="center" valign="top">11&#177;10&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="center" valign="top">0&#46;12&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of swollen joints&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="center" valign="top">4&#46;8&#177;5&#46;1&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="center" valign="top">5&#46;1&#177;4&#46;1&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="center" valign="top">0&#46;83&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DAS28&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="center" valign="top">3&#46;8&#177;1&#46;6&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="center" valign="top">4&#46;6&#177;1&#46;3&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="center" valign="top">0&#46;10&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ESR&#44; mm&#47;1<span class="elsevierStyleSup">st</span> hour&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="center" valign="top">26&#46;6&#177;26&#46;1&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="center" valign="top">27&#46;1&#177;15&#46;5&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="center" valign="top">0&#46;94&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CRP&#44; mg&#47;L&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="center" valign="top">8&#46;49&#177;9&#46;5&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="center" valign="top">15&#46;4&#177;17&#46;9&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="center" valign="top">0&#46;19&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  " align="left" valign="top"><span class="elsevierStyleBold">Ankylosing spondylitis &#40;n &#61; 31&#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="" 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><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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of painful joints&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="center" valign="top">5&#46;6&#177;13&#46;4&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="center" valign="top">3&#46;6&#177;4&#46;2&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="center" valign="top">0&#46;59&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of swollen joints&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="center" valign="top">1&#46;4&#177;1&#46;4&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="center" valign="top">1&#46;7&#177;2&#46;3&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="center" valign="top">0&#46;68&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BASDAI&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="center" valign="top">3&#46;48&#177;2&#46;01&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="center" valign="top">3&#46;47&#177;2&#46;43&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="center" valign="top">0&#46;99&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ESR&#44; mm&#47;1<span class="elsevierStyleSup">st</span> hour&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="center" valign="top">23&#177;27&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="center" valign="top">14&#177;16&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="center" valign="top">0&#46;27&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CRP&#44; mg&#47;L&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="center" valign="top">12&#46;6&#177;14&#46;5&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="center" valign="top">13&#46;2&#177;21&#46;1&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="center" valign="top">0&#46;94&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  " align="left" valign="top"><span class="elsevierStyleBold">Psoriatic arthritis &#40;n &#61; 11&#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="" 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><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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Morning stiffness &#40;minutes&#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="center" valign="top">0 &#40;0-20&#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="center" valign="top">17&#46;5 &#40;0-120&#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="center" valign="top">0&#46;14&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of painful joints&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="center" valign="top">5 &#40;0-8&#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="center" valign="top">3&#46;5 &#40;0-12&#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="center" valign="top">0&#46;93&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of swollen joints&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="center" valign="top">1 &#40;0-2&#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="center" valign="top">1 &#40;0-2&#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="center" valign="top">0&#46;77&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BASDAI&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="center" valign="top">2&#46;33 &#40;0-6&#46;98&#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="center" valign="top">4&#46;06 &#40;0&#46;27-5&#46;16&#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="center" valign="top">0&#46;48&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ESR&#44; mm&#47;1<span class="elsevierStyleSup">st</span> hour&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="center" valign="top">11&#46;5 &#40;3-76&#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="center" valign="top">23&#40;1-46&#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="center" valign="top">0&#46;73&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CRP&#44; mg&#47;L&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="center" valign="top">2 &#40;0&#46;2-19&#46;6&#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="center" valign="top">6&#46;8 &#40;1&#46;5-32&#46;5&#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="center" valign="top">0&#46;55&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  " align="left" valign="top"><span class="elsevierStyleBold">Rheumatic patients treated &#40;n &#61; 89&#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="" 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><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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anti-TNF and DMARD therapy duration &#40;months&#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="center" valign="top">15&#177;11&#46;7&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="center" valign="top">13&#46;6&#177;9&#46;7&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="center" valign="top">0&#46;55&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glucocorticoid use&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="center" valign="top">15 &#40;44&#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="center" valign="top">35 &#40;64&#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="center" valign="top">0&#46;08&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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Methotrexate use&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="center" valign="top">26 &#40;76&#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="center" valign="top">33 &#40;60&#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="center" valign="top">0&#46;17&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  " align="left" valign="top" style="border-bottom: 2px solid black"><span class="elsevierStyleHsp" style=""></span>Number of DMARDs&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="center" valign="top" style="border-bottom: 2px solid black">1&#46;1&#177;0&#46;7&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="center" valign="top" style="border-bottom: 2px solid black">0&#46;9&#177;0&#46;7&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="center" valign="top" style="border-bottom: 2px solid black">0&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Disease activity parameters and treatments in patients with rheumatic diseases undergoing anti-TNF and DMARD therapies with and without microsporidia infection&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl3"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Results are presented as n &#40;&#37;&#41;&#59; DMARDs - disease-modifying anti-rheumatic drugs&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
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                0 => """
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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
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">Clinical manifestations&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="center" valign="top" scope="col">Patients with microsporidia &#40;n &#61; 34&#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="center" valign="top" scope="col">Patients without microsporidia &#40;n &#61; 55&#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="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value&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  " align="left" valign="top">Abdominal pain&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="char" valign="top">10 &#40;29&#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="char" valign="top">10 &#40;18&#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="char" valign="top">0&#46;296&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  " align="left" valign="top">Diarrhea&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="char" valign="top">10 &#40;29&#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="char" valign="top">7 &#40;13&#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="char" valign="top">0&#46;094&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  " align="left" valign="top">Weight loss&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="char" valign="top">2 &#40;6&#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="char" valign="top">8 &#40;15&#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="char" valign="top">0&#46;306&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  " align="left" valign="top">Nausea&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="char" valign="top">8 &#40;24&#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="char" valign="top">14 &#40;25&#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="char" valign="top">1&#46;0&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  " align="left" valign="top">Vomit&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="char" valign="top">6 &#40;18&#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="char" valign="top">8 &#40;15&#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="char" valign="top">0&#46;768&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  " align="left" valign="top">Flatulence&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="char" valign="top">6 &#40;18&#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="char" valign="top">19 &#40;35&#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="char" valign="top">0&#46;096&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  " align="left" valign="top">Dysentery&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="char" valign="top">2 &#40;6&#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="char" valign="top">0 &#40;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="char" valign="top">0&#46;143&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  " align="left" valign="top">Tenesmus&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="char" valign="top">0 &#40;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="char" valign="top">4 &#40;7&#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="char" valign="top">0&#46;294&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  " align="left" valign="top">Obstipation&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="char" valign="top">6 &#40;18&#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="char" valign="top">9 &#40;16&#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="char" valign="top">1&#46;0&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  " align="left" valign="top">Loss of appetite&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="char" valign="top">7 &#40;21&#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="char" valign="top">6 &#40;11&#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="char" valign="top">0&#46;231&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  " align="left" valign="top">Hematochezia&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="char" valign="top">2 &#40;6&#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="char" valign="top">5 &#40;9&#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="char" valign="top">0&#46;704&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  " align="left" valign="top">Worm elimination&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="char" valign="top">0 &#40;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="char" valign="top">5 &#40;9&#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="char" valign="top">0&#46;152&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  " align="left" valign="top">Wheezing&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="char" valign="top">8 &#40;24&#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="char" valign="top">5 &#40;9&#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="char" valign="top">0&#46;072&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  " align="left" valign="top">Thoracic pain&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="char" valign="top">8 &#40;24&#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="char" valign="top">6 &#40;11&#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="char" valign="top">0&#46;139&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  " align="left" valign="top">Hemoptysis&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="char" valign="top">2 &#40;6&#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="char" valign="top">2 &#40;4&#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="char" valign="top">0&#46;635&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  " align="left" valign="top">Exanthema&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="char" valign="top">2 &#40;6&#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="char" valign="top">10 &#40;18&#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="char" valign="top">0&#46;121&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  " align="left" valign="top">Abdominal distension&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="char" valign="top">2 &#40;6&#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="char" valign="top">15 &#40;27&#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="char" valign="top">0&#46;013&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  " align="left" valign="top">Adynamia&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="char" valign="top">11 &#40;32&#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="char" valign="top">34 &#40;62&#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="char" valign="top">0&#46;009&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  " align="left" valign="top">Any gastrointestinal symptom&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="char" valign="top">29 &#40;85&#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="char" valign="top">47 &#40;85&#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="char" valign="top">1&#46;0&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  " align="left" valign="top" style="border-bottom: 2px solid black">Systemic dissemination&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="char" valign="top" style="border-bottom: 2px solid black">0 &#40;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="char" valign="top" style="border-bottom: 2px solid black">0 &#40;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="char" valign="top" style="border-bottom: 2px solid black">1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Clinical manifestations in patients with rheumatic diseases undergoing anti-TNF and DMARD therapies with and without microsporidia infection&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:37 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical significance of enteric protozoa in the immunosuppressed human population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              D Stark \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JL Barratt \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S van Hal \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              D Marriott \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              J Harkness \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              JT Ellis \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1128/CMR.00017-09"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Microbiol Rev"
                        "fecha" => "2009"
                        "volumen" => "22"
                        "paginaInicial" => "634"
                        "paginaFinal" => "650"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19822892"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1128/CMR.00017-09"
                      "WWW" => array:1 [
                        "link" => "10&#46;1128&#47;CMR&#46;00017-09"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microsporidiosis&#58; an emerging and opportunistic infection in humans and animals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              ES Didier \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.actatropica.2005.01.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Trop"
                        "fecha" => "2005"
                        "volumen" => "94"
                        "paginaInicial" => "61"
                        "paginaFinal" => "76"
                        "link" => array:1 [
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