Tuberculosis: Plasma levels of vitamin D and its relation with infection and disease

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Caused by Mycobacterium tuberculosis (M. tuberculosis), it is a respiratory infection spread by droplets that carry bacilli to the lower respiratory tract which, under adequate circumstances, may be highly contagious. Once located in the pulmonary tissue, M. tuberculosis is detected by the alveolar macrophage toll-like receptors. This triggers an immune response to the infection that results in the activation of a highly complex set of processes. Several researchers have demonstrated that there is a possible genetic susceptibility towards developing the disease as occurs when there are mutations in the NRAMP1 and MCP-1 genes, the gamma interferon and vitamin D (vitD) receptors, among others.In 1983, the vitD receptor and its presence in immunomodulatory cells were discovered, revealing the immune actions of vitD and the potential implications of this for human disease. In a growing number of new studies, it has been suggested that vitD could consistently intervene not only in the immune system but also in the cardiovascular system and that it could be of use in cancer prevention. In several cross-sectional studies, low vitD plasma concentrations have been observed in patients with active or latent tuberculous infection, though it has not been possible to demonstrate a cause-effect relation. Other studies have confirmed the intervention of vitD metabolites in immunoregulation processes, since these are part of the first line of defence against tuberculosis through the expression of an antimicrobial peptide, cathelicidin. These metabolites are modulators of the macrophage function and have demonstrated in vitro their capacity to inhibit intracellular growth of M. tuberculosis. Moreover, experimental studies have determined that vitD therapy improves the immune response to M. tuberculosis.The objective of the present study is to assess the clinical and epidemiological features of a cohort of patients for whom vitD plasma concentrations had been determined and to study the relation, if any, between vitD values and tuberculosis, paying special attention to the form of presentation.Patients and methodFrom January 2010 to June 2012, a retrospective observational study was conducted in the Tuberculosis Unit of the Hospital del Mar, Barcelona, Spain. This study analysed the demographic, clinical and microbiological variables of patients diagnosed with active tuberculosis and their contact with latent tuberculosis infection (LTBI) for whom 25-hydroxy-vitD plasma concentration had been determined by electrochemiluminescence. The optimal reference range was between 30 and 80ng/ml. For the purpose of the study, vitD deficiency was defined as any level lower than 20ng/ml and, in particular, severe vitD deficiency included all measures below 10ng/ml. Values between 20 and 30ng/ml were considered insufficient, but not clearly deficient<a class="elsevierStyleCrossRef" href="#bib0055">1</a>.Diagnosis of tuberculosis was established in patients with in-culture growth of M. tuberculosis complex, positive polymerase chain reaction and/or compatible cytology or biopsy of an organic fluid or tissue sample. A positive result in the tuberculin test (≥5 mm induration) and/or quantiferon test (≥0.35 IU/ml) conducted on a person with a history of recent contact with a patient diagnosed with active tuberculosis was considered LTBI<a class="elsevierStyleCrossRef" href="#bib0060">2</a>.The disease was classified as active by taking in account the anatomical location (pulmonary, pleural, peritoneal, meningeal, lymphatic, disseminated/miliary and other locations) and severity, and patients were respectively grouped as pulmonary/extrapulmonary and severe/non-severe; severe forms included tuberculous meningitis and disseminated tuberculosis. Initially, as many as 5 different ethnic groups were identified: European Caucasian, non-European Caucasian, Mongoloid (Asian), black (African) and mixed race; these were later re-classified as the categorical variable of white (European Caucasian) and non-white (the rest). The Charlson comorbidity index was used to assess the presence of baseline diseases.Descriptive analysis of the variables was conducted by calculating the mean and median values. Categorical variables were analysed using the chi square test and quantitative variables were analysed using the Mann-Whitney U test. Moreover, logistic regression analysis was carried out for the adjusted calculation of the risk associated with vitD deficiency. For the statistical study, SPSS 16 (SPSS Inc. 233 South Wacker Drive, Chicago, IL, U.S.A.) was used.ResultsFrom January 1, 2010, to June 30, 2012, the Hospital del Mar informed the Barcelona Tuberculosis Control and Prevention Program (Programa de Control y Prevención de Tuberculosis) of 212 new cases of tuberculosis, of which 152 cases (72%) had microbiological confirmation. The present study included 86 patients with active tuberculosis and 80 contacts with LTBI, in whom vitD plasma concentration had been determined. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 1</a> shows the descriptive analysis (univariate) and the risk factors associated with active tuberculosis (multivariate analysis). Of the 86 patients with active tuberculosis, 44 (51.2%) were Caucasian and 51 (59.3%) were male. The mean age (SD) of the group was 41.4 (18.2) years. The mean vitD concentration (SD) was 12.4 (9.3)ng/ml, and the median was 9.2 (interquartile range 5.2-19). In this group of patients, a vitD deficiency was detected (<20ng/ml) in 65 cases (75.6%), of which 47 (54.7%) had a severe deficiency. In the logistic regression analysis, factors associated with active tuberculosis were vitD deficiency <10ng/ml (odds ratio [OR] 2.02, 95% confidence interval [95% CI] 1.04-3.93; p=0.04), male sex (OR 1.9; 95% CI 0.96-3.71; p=0.06) and non-Caucasian race (OR 0.7; 95% CI 0.34-1.42; p=0.3). Severe vitD deficiency was found to be an independent risk factor for active disease.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The anatomical location of tuberculosis was pulmonary in 42 cases, lymphatic in 21, disseminated/miliary in 7, meningeal in 5, and other serum locations (pleural, peritoneal) in 5. Six patients had tuberculosis in other locations. The proportion of patients with severe vitD deficiency was greater in cases with extrapulmonary location (p=0.009). The multiple logistic regression analysis (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) to determine factors associated with extrapulmonary forms selected vitD values <10ng/ml (OR 2.38; 95% CI 0.93-6.06; p=0.07) and non-Caucasian race (OR 2.75; 95% CI 1.08-7; p=0.03) as independent risk factors for extrapulmonary location of tuberculosis.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Finally, <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a> shows that, out of 15 patients with severe active tuberculosis, 7 (46.7%) had severe vitD deficiency and that, out of 71 patients with less severe forms of tuberculosis, 40 had severe vitD deficiency (p=0.5).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>DiscussionMany studies suggest that vitD deficiency is associated with a greater susceptibility towards infection caused by M. tuberculosis<a class="elsevierStyleCrossRef" href="#bib0065">3</a>. Sita-Lumsden et al.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> proved that patients had lower concentrations than their relatives with similar diet and sun exposure, regardless of the degree of cutaneous pigmentation. Moreover, these authors indicated that vitD plasma levels in healthy relatives increased during the summer, unlike those of the patients. Noaham and Clarke<a class="elsevierStyleCrossRef" href="#bib0075">5</a> conducted a meta-analysis of 151 articles published between 1980 and 2006 that led to the conclusion that there was a significant relation between tuberculosis and vitD deficiency. However, they noticed a lack of prospective studies to help them determine how this relation occurred.In terms of therapy, vitD had already been used in the treatment of tuberculosis during the pre-antibiotic era<a class="elsevierStyleCrossRef" href="#bib0080">6</a>. However, its possible reintroduction is related to the genetic identification of patients with polymorphisms in the human vitD receptor, such as the Taql tt genotype, who have shown a significant reduction in the sputum conversion rate following the incorporating 2.5 mg/day of vitD as a supplement to their antituberculous treatment<a class="elsevierStyleCrossRef" href="#bib0085">7</a>. Furthermore, the therapeutic use of vitD is limited by its possible side effects, including the development of inflammatory reactions and iatrogenic hypercalcaemia if high doses are used (>100,000 IU/day)<a class="elsevierStyleCrossRef" href="#bib0090">8</a>. There is no evidence of other adverse events in daily, weekly, or monthly vitD administration regimes. Hence, scientists and clinicians recommend maintaining 25-hydroxy-vitDlevels at a minimum of 30ng/ml<a class="elsevierStyleCrossRef" href="#bib0095">9</a>.The main contribution of this study is that, on comparing a group of patients with their contacts, severe vitD deficiency seems to be an independent risk factor for active tuberculosis. Furthermore, we have observed an almost statistically significant tendency towards the risk of having extrapulmonary tuberculosis in patients with the lowest concentrations of this hormone, which leads us to believe that this group of patients will most commonly have the most severe clinical forms of the disease.The retrospective design and the relatively low number of patients and infected individuals in this study make it impossible to determine whether vitD deficiency favours the development of active tuberculosis or if active tuberculosis lowers vitD values. However, no causality conclusions have been obtained from larger studies with a significantly higher number of patients, either. In this case, it was possible to analyse simultaneously patients with active tuberculosis and their contacts with LTBI, that is to say, individuals who were possibly exposed to the same source of contagion and who belong to the same race group and the same socioeconomic stratum. The different behaviour of the infection caused by M. tuberculosis in the two groups, patients and contacts, suggests that higher values of vitD could have a protective role in relation to the development of active tuberculosis, as indicated elsewhere<a class="elsevierStyleCrossRef" href="#bib0100">10</a>. There was no statistically significant relation between vitD values and the extrapulmonary clinical presentation or severity of the disease. However, we should indicate that the number of meningeal and disseminated forms was very low.A further limitation that ought to be considered is that vitD determinations were not obtained at the same time of the year. Vitamin D values are known to vary according to the season. Even so, it is reasonable to assume that the distribution of these differences would affect patients and contacts with no active disease in a similar manner, given that family environment studies are conducted within a time framework that is very close to the reference case diagnosis.It has been demonstrated that there is a connection between vitD deficiency and the risk of developing tuberculosis. Studies conducted to date do not allow us to determine an underlying cause-effect relation for this connection. Interventional, prospective and randomised studies of an adequate sample size would be necessary to determine whether vitD deficiency supplements have a protective effect against the development of tuberculosis in areas and/or communities with a high prevalence of the disease.Conflict of interestThe authors declare that there are no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres568373" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec585728" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres568374" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec585727" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Patients and method" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-06-10" "fechaAceptado" => "2013-09-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec585728" "palabras" => array:3 [ 0 => "Tuberculosis" 1 => "Vitamin D" 2 => "Plasma concentration" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec585727" "palabras" => array:3 [ 0 => "Tuberculosis" 1 => "Vitamina D" 2 => "Concentración plasmática" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and objectiveVitamin D (vitD) is involved in the phosphor-calcium metabolism and bone pathology, but also in inflammatory and infectious processes such as tuberculosis. The present study evaluates the clinical and epidemiological aspects of active tuberculosis cases and latently infected contacts in whom plasma concentrations of vitD were obtained to determine whether the deficiency of vitD is a risk factor to develop active tuberculosis, especially the more severe forms. MethodObservational, retrospective study that included 86 tuberculosis patients and 80 contacts with latent infection in a 2-year period. ResultsWhen comparing active tuberculosis cases with latent infection contacts, deficiency of vitD (vitD levels <10ng/mL, odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.04–3.93), male sex (OR: 1.9, 95% CI: 0.96–3.71) and non-white race (OR: 0.7, 95% CI: 0.34–1.42) were factors independently associated with the diagnosis of tuberculosis. ConclusionDespite the limited number of subjects studied, there was an association between severe deficit of vitD and the presentation of tuberculosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Fundamento y objetivoLa vitamina D (vitD) interviene en el metabolismo fosfocálcico y la enfermedad ósea, pero también en procesos inflamatorio-infecciosos como la tuberculosis. En el presente estudio se evalúan aspectos clínicos y epidemiológicos de enfermos e infectados por Mycobacterium tuberculosis en quienes se obtuvieron concentraciones plasmáticas de vitD para determinar si existe relación entre el déficit de vitD y el riesgo de desarrollar tuberculosis activa, especialmente las formas más graves. MétodoEstudio observacional retrospectivo que incluyó a 86 pacientes con tuberculosis activa y 80 contactos con infección latente, visitados en una unidad especializada, en un período de 2 años. ResultadosAl comparar enfermos con infectados, el déficit de vitD (valores de vitD<10ng/ml; odds ratio [OR] 2,02; intervalo de confianza del 95% [IC 95%] 1,04-3,93), el sexo varón (OR 1,9; IC 95% 0,96-3,71) y la raza no caucásica (OR 0,7; IC 95% 0,34-1,42) fueron los factores independientemente asociados al diagnóstico de tuberculosis. ConclusiónA pesar del limitado número de sujetos estudiados, se ha detectado una asociación entre el déficit grave de vitD y la forma de presentación de la tuberculosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Esteve Palau E, Sánchez Martínez F, Knobel Freud H, López Colomés J L, Diez Pérez A. Infección y enfermedad tuberculosa en relación con concentraciones plasmáticas de vitamina D. Med Clin (Barc). 2015;144:111–114." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "SD: standard deviation; 95% CI: 95% confidence interval; LTBI: latent tuberculosis infection; NS: non-significant; OR: odds ratio; TB: tuberculosis; VitD: vitamin D.(*) Interquartile range." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TB cases (N=86) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LTBI contacts (N=80) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean age (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 (18.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 (16.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">-Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.4 (9.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.8 (11.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">-Median(*) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.2 (5.3-19.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.85 (7.1-22.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD <20 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65 (75.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 (72.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD <10 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 (54.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (37.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.02 (1.04-3.93) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Male patients (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 (59.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 (40.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (0.96-3.71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Female patients (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 (40.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 (56.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top">Race</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Caucasian (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 (51.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 (53.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Non-Caucasian (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 (48.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 (46.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 (0.34-1.42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab924979.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison between active tuberculosis (cases) and latent infection (contacts)." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "95% CI: 95% confidence interval; OR: odds ratio; VitD: vitamin D." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Factor \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pulmonary N=42 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Extrapulmonary N=44 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD <10 ng/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">N (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.38 (0.93-6.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD ≥10 ng/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">N (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (68) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Caucasian \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Non-Caucasian \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.75 (1.08-7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab924978.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Anatomical location of tuberculosis and logistic regression analysis of factors associated with anatomical location." ] ] 2 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "TB: tuberculosis; VitD: vitamin D." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Severe TB \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Non-severe TB \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD < 10 ng/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VitD ≥ 10 ng/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (17.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71 (82.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab924977.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Vitamin D deficiency: comparison between severe and non-severe forms of tuberculosis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.K. 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Tuberculosis: Plasma levels of vitamin D and its relation with infection and disease

Infección y enfermedad tuberculosa en relación con concentraciones plasmáticas de vitamina D

Erika Esteve Palaua, Francesca Sánchez Martíneza,

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97816@parcdesalutmar.cat

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, Hernando Knobel Freuda, José-Luís López Colomésa, Adolfo Diez Pérezb

a Servicio de Enfermedades Infecciosas, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain

b Servicio de Medicina Interna, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain

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    "cabecera" => "<span class="elsevierStyleTextfn">Brief report</span>"
    "titulo" => "Tuberculosis&#58; Plasma levels of vitamin D and its relation with infection and disease"
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        "autoresLista" => "Erika Esteve Palau, Francesca S&#225;nchez Mart&#237;nez, Hernando Knobel Freud, Jos&#233;-Lu&#237;s L&#243;pez Colom&#233;s, Adolfo Diez P&#233;rez"
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            "entidad" => "Servicio de Enfermedades Infecciosas&#44; Hospital del Mar&#44; Parc de Salut Mar&#44; Barcelona&#44; Spain"
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        "titulo" => "Infecci&#243;n y enfermedad tuberculosa en relaci&#243;n con concentraciones plasm&#225;ticas de vitamina D"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberculosis is a disease with a multifactorial physiopathology that is considered a worldwide health condition due to its high prevalence and morbidity and mortality&#46; Caused by <span class="elsevierStyleItalic">Mycobacterium tuberculosis &#40;M&#46; tuberculosis&#41;</span>&#44; it is a respiratory infection spread by droplets that carry bacilli to the lower respiratory tract which&#44; under adequate circumstances&#44; may be highly contagious&#46; Once located in the pulmonary tissue&#44; <span class="elsevierStyleItalic">M&#46; tuberculosis</span> is detected by the alveolar macrophage toll-like receptors&#46; This triggers an immune response to the infection that results in the activation of a highly complex set of processes&#46; Several researchers have demonstrated that there is a possible genetic susceptibility towards developing the disease as occurs when there are mutations in the <span class="elsevierStyleItalic">NRAMP1</span> and <span class="elsevierStyleItalic">MCP-1</span> genes&#44; the gamma interferon and vitamin D &#40;vitD&#41; receptors&#44; among others&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 1983&#44; the vitD receptor and its presence in immunomodulatory cells were discovered&#44; revealing the immune actions of vitD and the potential implications of this for human disease&#46; In a growing number of new studies&#44; it has been suggested that vitD could consistently intervene not only in the immune system but also in the cardiovascular system and that it could be of use in cancer prevention&#46; In several cross-sectional studies&#44; low vitD plasma concentrations have been observed in patients with active or latent tuberculous infection&#44; though it has not been possible to demonstrate a cause-effect relation&#46; Other studies have confirmed the intervention of vitD metabolites in immunoregulation processes&#44; since these are part of the first line of defence against tuberculosis through the expression of an antimicrobial peptide&#44; cathelicidin&#46; These metabolites are modulators of the macrophage function and have demonstrated <span class="elsevierStyleItalic">in vitro</span> their capacity to inhibit intracellular growth of <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; Moreover&#44; experimental studies have determined that vitD therapy improves the immune response to <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objective of the present study is to assess the clinical and epidemiological features of a cohort of patients for whom vitD plasma concentrations had been determined and to study the relation&#44; if any&#44; between vitD values and tuberculosis&#44; paying special attention to the form of presentation&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and method</span><p id="par0020" class="elsevierStylePara elsevierViewall">From January 2010 to June 2012&#44; a retrospective observational study was conducted in the Tuberculosis Unit of the Hospital del Mar&#44; Barcelona&#44; Spain&#46; This study analysed the demographic&#44; clinical and microbiological variables of patients diagnosed with active tuberculosis and their contact with latent tuberculosis infection &#40;LTBI&#41; for whom 25-hydroxy-vitD plasma concentration had been determined by electrochemiluminescence&#46; The optimal reference range was between 30 and 80<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; For the purpose of the study&#44; vitD deficiency was defined as any level lower than 20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and&#44; in particular&#44; severe vitD deficiency included all measures below 10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Values between 20 and 30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml were considered insufficient&#44; but not clearly deficient<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis of tuberculosis was established in patients with in-culture growth of <span class="elsevierStyleItalic">M&#46; tuberculosis complex</span>&#44; positive polymerase chain reaction and&#47;or compatible cytology or biopsy of an organic fluid or tissue sample&#46; A positive result in the tuberculin test &#40;&#8805;5&#160;mm induration&#41; and&#47;or quantiferon test &#40;&#8805;0&#46;35&#160;IU&#47;ml&#41; conducted on a person with a history of recent contact with a patient diagnosed with active tuberculosis was considered LTBI<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The disease was classified as active by taking in account the anatomical location &#40;pulmonary&#44; pleural&#44; peritoneal&#44; meningeal&#44; lymphatic&#44; disseminated&#47;miliary and other locations&#41; and severity&#44; and patients were respectively grouped as pulmonary&#47;extrapulmonary and severe&#47;non-severe&#59; severe forms included tuberculous meningitis and disseminated tuberculosis&#46; Initially&#44; as many as 5&#160;different ethnic groups were identified&#58; European Caucasian&#44; non-European Caucasian&#44; Mongoloid &#40;Asian&#41;&#44; black &#40;African&#41; and mixed race&#59; these were later re-classified as the categorical variable of white &#40;European Caucasian&#41; and non-white &#40;the rest&#41;&#46; The Charlson comorbidity index was used to assess the presence of baseline diseases&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Descriptive analysis of the variables was conducted by calculating the mean and median values&#46; Categorical variables were analysed using the chi square test and quantitative variables were analysed using the Mann-Whitney U test&#46; Moreover&#44; logistic regression analysis was carried out for the adjusted calculation of the risk associated with vitD deficiency&#46; For the statistical study&#44; SPSS 16 &#40;SPSS Inc&#46; 233 South Wacker Drive&#44; Chicago&#44; IL&#44; U&#46;S&#46;A&#46;&#41; was used&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">From January 1&#44; 2010&#44; to June 30&#44; 2012&#44; the Hospital del Mar informed the Barcelona Tuberculosis Control and Prevention Program &#40;Programa de Control y Prevenci&#243;n de Tuberculosis&#41; of 212 new cases of tuberculosis&#44; of which 152&#160;cases &#40;72&#37;&#41; had microbiological confirmation&#46; The present study included 86&#160;patients with active tuberculosis and 80&#160;contacts with LTBI&#44; in whom vitD plasma concentration had been determined&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 1</a> shows the descriptive analysis &#40;univariate&#41; and the risk factors associated with active tuberculosis &#40;multivariate analysis&#41;&#46; Of the 86&#160;patients with active tuberculosis&#44; 44 &#40;51&#46;2&#37;&#41; were Caucasian and 51 &#40;59&#46;3&#37;&#41; were male&#46; The mean age &#40;SD&#41; of the group was 41&#46;4 &#40;18&#46;2&#41; years&#46; The mean vitD concentration &#40;SD&#41; was 12&#46;4 &#40;9&#46;3&#41;<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; and the median was 9&#46;2 &#40;interquartile range 5&#46;2-19&#41;&#46; In this group of patients&#44; a vitD deficiency was detected &#40;&#60;20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; in 65&#160;cases &#40;75&#46;6&#37;&#41;&#44; of which 47 &#40;54&#46;7&#37;&#41; had a severe deficiency&#46; In the logistic regression analysis&#44; factors associated with active tuberculosis were vitD deficiency &#60;10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;odds ratio &#91;OR&#93;&#160;2&#46;02&#44; 95&#37; confidence interval &#91;95&#37; CI&#93; 1&#46;04-3&#46;93&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#44; male sex &#40;OR 1&#46;9&#59; 95&#37; CI 0&#46;96-3&#46;71&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06&#41; and non-Caucasian race &#40;OR 0&#46;7&#59; 95&#37; CI 0&#46;34-1&#46;42&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#41;&#46; Severe vitD deficiency was found to be an independent risk factor for active disease&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The anatomical location of tuberculosis was pulmonary in 42&#160;cases&#44; lymphatic in 21&#44; disseminated&#47;miliary in 7&#44; meningeal in 5&#44; and other serum locations &#40;pleural&#44; peritoneal&#41; in 5&#46; Six patients had tuberculosis in other locations&#46; The proportion of patients with severe vitD deficiency was greater in cases with extrapulmonary location &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41;&#46; The multiple logistic regression analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; to determine factors associated with extrapulmonary forms selected vitD values &#60;10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;OR 2&#46;38&#59; 95&#37; CI 0&#46;93-6&#46;06&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;07&#41; and non-Caucasian race &#40;OR 2&#46;75&#59; 95&#37; CI 1&#46;08-7&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41; as independent risk factors for extrapulmonary location of tuberculosis&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Finally&#44; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a> shows that&#44; out of 15 patients with severe active tuberculosis&#44; 7 &#40;46&#46;7&#37;&#41; had severe vitD deficiency and that&#44; out of 71 patients with less severe forms of tuberculosis&#44; 40 had severe vitD deficiency &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">Many studies suggest that vitD deficiency is associated with a greater susceptibility towards infection caused by <span class="elsevierStyleItalic">M&#46; tuberculosis</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a>&#46; Sita-Lumsden et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> proved that patients had lower concentrations than their relatives with similar diet and sun exposure&#44; regardless of the degree of cutaneous pigmentation&#46; Moreover&#44; these authors indicated that vitD plasma levels in healthy relatives increased during the summer&#44; unlike those of the patients&#46; Noaham and Clarke<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> conducted a meta-analysis of 151&#160;articles published between 1980 and 2006 that led to the conclusion that there was a significant relation between tuberculosis and vitD deficiency&#46; However&#44; they noticed a lack of prospective studies to help them determine how this relation occurred&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In terms of therapy&#44; vitD had already been used in the treatment of tuberculosis during the pre-antibiotic era<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a>&#46; However&#44; its possible reintroduction is related to the genetic identification of patients with polymorphisms in the human vitD receptor&#44; such as the <span class="elsevierStyleItalic">Taql</span> tt genotype&#44; who have shown a significant reduction in the sputum conversion rate following the incorporating 2&#46;5&#160;mg&#47;day of vitD as a supplement to their antituberculous treatment<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a>&#46; Furthermore&#44; the therapeutic use of vitD is limited by its possible side effects&#44; including the development of inflammatory reactions and iatrogenic hypercalcaemia if high doses are used &#40;&#62;100&#44;000&#160;IU&#47;day&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a>&#46; There is no evidence of other adverse events in daily&#44; weekly&#44; or monthly vitD administration regimes&#46; Hence&#44; scientists and clinicians recommend maintaining 25-hydroxy-vitDlevels at a minimum of 30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The main contribution of this study is that&#44; on comparing a group of patients with their contacts&#44; severe vitD deficiency seems to be an independent risk factor for active tuberculosis&#46; Furthermore&#44; we have observed an almost statistically significant tendency towards the risk of having extrapulmonary tuberculosis in patients with the lowest concentrations of this hormone&#44; which leads us to believe that this group of patients will most commonly have the most severe clinical forms of the disease&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The retrospective design and the relatively low number of patients and infected individuals in this study make it impossible to determine whether vitD deficiency favours the development of active tuberculosis or if active tuberculosis lowers vitD values&#46; However&#44; no causality conclusions have been obtained from larger studies with a significantly higher number of patients&#44; either&#46; In this case&#44; it was possible to analyse simultaneously patients with active tuberculosis and their contacts with LTBI&#44; that is to say&#44; individuals who were possibly exposed to the same source of contagion and who belong to the same race group and the same socioeconomic stratum&#46; The different behaviour of the infection caused by <span class="elsevierStyleItalic">M&#46; tuberculosis</span> in the two groups&#44; patients and contacts&#44; suggests that higher values of vitD could have a protective role in relation to the development of active tuberculosis&#44; as indicated elsewhere<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a>&#46; There was no statistically significant relation between vitD values and the extrapulmonary clinical presentation or severity of the disease&#46; However&#44; we should indicate that the number of meningeal and disseminated forms was very low&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A further limitation that ought to be considered is that vitD determinations were not obtained at the same time of the year&#46; Vitamin D values are known to vary according to the season&#46; Even so&#44; it is reasonable to assume that the distribution of these differences would affect patients and contacts with no active disease in a similar manner&#44; given that family environment studies are conducted within a time framework that is very close to the reference case diagnosis&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">It has been demonstrated that there is a connection between vitD deficiency and the risk of developing tuberculosis&#46; Studies conducted to date do not allow us to determine an underlying cause-effect relation for this connection&#46; Interventional&#44; prospective and randomised studies of an adequate sample size would be necessary to determine whether vitD deficiency supplements have a protective effect against the development of tuberculosis in areas and&#47;or communities with a high prevalence of the disease&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vitamin D &#40;vitD&#41; is involved in the phosphor-calcium metabolism and bone pathology&#44; but also in inflammatory and infectious processes such as tuberculosis&#46; The present study evaluates the clinical and epidemiological aspects of active tuberculosis cases and latently infected contacts in whom plasma concentrations of vitD were obtained to determine whether the deficiency of vitD is a risk factor to develop active tuberculosis&#44; especially the more severe forms&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Observational&#44; retrospective study that included 86 tuberculosis patients and 80 contacts with latent infection in a 2-year period&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">When comparing active tuberculosis cases with latent infection contacts&#44; deficiency of vitD &#40;vitD levels &#60;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; odds ratio &#91;OR&#93;&#58; 2&#46;02&#44; 95&#37; confidence interval &#91;CI&#93;&#58; 1&#46;04&#8211;3&#46;93&#41;&#44; male sex &#40;OR&#58; 1&#46;9&#44; 95&#37; CI&#58; 0&#46;96&#8211;3&#46;71&#41; and non-white race &#40;OR&#58; 0&#46;7&#44; 95&#37; CI&#58; 0&#46;34&#8211;1&#46;42&#41; were factors independently associated with the diagnosis of tuberculosis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Despite the limited number of subjects studied&#44; there was an association between severe deficit of vitD and the presentation of tuberculosis&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La vitamina D &#40;vitD&#41; interviene en el metabolismo fosfoc&#225;lcico y la enfermedad &#243;sea&#44; pero tambi&#233;n en procesos inflamatorio-infecciosos como la tuberculosis&#46; En el presente estudio se eval&#250;an aspectos cl&#237;nicos y epidemiol&#243;gicos de enfermos e infectados por <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> en quienes se obtuvieron concentraciones plasm&#225;ticas de vitD para determinar si existe relaci&#243;n entre el d&#233;ficit de vitD y el riesgo de desarrollar tuberculosis activa&#44; especialmente las formas m&#225;s graves&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional retrospectivo que incluy&#243; a 86 pacientes con tuberculosis activa y 80 contactos con infecci&#243;n latente&#44; visitados en una unidad especializada&#44; en un per&#237;odo de 2 a&#241;os&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Al comparar enfermos con infectados&#44; el d&#233;ficit de vitD &#40;valores de vitD<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; odds ratio &#91;OR&#93; 2&#44;02&#59; intervalo de confianza del 95&#37; &#91;IC 95&#37;&#93; 1&#44;04-3&#44;93&#41;&#44; el sexo var&#243;n &#40;OR 1&#44;9&#59; IC 95&#37; 0&#44;96-3&#44;71&#41; y la raza no cauc&#225;sica &#40;OR 0&#44;7&#59; IC 95&#37; 0&#44;34-1&#44;42&#41; fueron los factores independientemente asociados al diagn&#243;stico de tuberculosis&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A pesar del limitado n&#250;mero de sujetos estudiados&#44; se ha detectado una asociaci&#243;n entre el d&#233;ficit grave de vitD y la forma de presentaci&#243;n de la tuberculosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Fundamento y objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Esteve Palau E&#44; S&#225;nchez Mart&#237;nez F&#44; Knobel Freud H&#44; L&#243;pez Colom&#233;s J L&#44; Diez P&#233;rez A&#46; Infecci&#243;n y enfermedad tuberculosa en relaci&#243;n con concentraciones plasm&#225;ticas de vitamina D&#46; Med Clin &#40;Barc&#41;&#46; 2015&#59;144&#58;111&#8211;114&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; 95&#37; CI&#58; 95&#37; confidence interval&#59; LTBI&#58; latent tuberculosis infection&#59; NS&#58; non-significant&#59; OR&#58; odds ratio&#59; TB&#58; tuberculosis&#59; VitD&#58; vitamin&#160;D&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#40;&#42;&#41; Interquartile range&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TB cases &#40;N&#61;86&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LTBI contacts &#40;N&#61;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Mean age &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43 &#40;16&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">VitD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">-Mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;4 &#40;9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;8 &#40;11&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">-Median&#40;&#42;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;2 &#40;5&#46;3-19&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;85 &#40;7&#46;1-22&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">VitD &#60;20 &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65 &#40;75&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58 &#40;72&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">VitD &#60;10 &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47 &#40;54&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;02 &#40;1&#46;04-3&#46;93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Male patients &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51 &#40;59&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35 &#40;40&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9 &#40;0&#46;96-3&#46;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Female patients &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35 &#40;40&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45 &#40;56&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top">Race</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Caucasian &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44 &#40;51&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43 &#40;53&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Non-Caucasian &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42 &#40;48&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37 &#40;46&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7 &#40;0&#46;34-1&#46;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab924979.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Comparison between active tuberculosis &#40;cases&#41; and latent infection &#40;contacts&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">95&#37; CI&#58; 95&#37; confidence interval&#59; OR&#58; odds ratio&#59; VitD&#58; vitamin&#160;D&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pulmonary N&#61;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Extrapulmonary N&#61;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">VitD &#60;10&#160;ng&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">N &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;38 &#40;0&#46;93-6&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">VitD &#8805;10&#160;ng&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">N &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Caucasian</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&nbsp;\t\t\t\t\t\t\n
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                          "autores" => array:1 [
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Article information

ISSN: 23870206
Original language: English

DOI:10.1016/j.medcle.2015.05.003

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