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"en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1727 "Ancho" => 1417 "Tamanyo" => 213033 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Influence of the reagents’ concentrations in the PCR products obtained in optimization experiments.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ivanete De Lima Sampaio, Ana Karla Lima Freire, Mauricio Morishi Ogusko, Júlia Ignez Salem, João Vicente Braga De Souza" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Ivanete" "apellidos" => "De Lima Sampaio" ] 1 => array:2 [ "nombre" => "Ana Karla" "apellidos" => "Lima Freire" ] 2 => array:2 [ "nombre" => "Mauricio" "apellidos" => "Morishi Ogusko" ] 3 => array:2 [ "nombre" => "Júlia" "apellidos" => "Ignez Salem" ] 4 => array:2 [ "nombre" => "João Vicente" "apellidos" => "Braga De Souza" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140611000428?idApp=UINPBA00004N" "url" => "/11301406/0000002900000001/v1_201305061404/S1130140611000428/v1_201305061404/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Characterization of clinical isolates of the <span class="elsevierStyleItalic">Cryptococcus neoformans-Cryptococcus gattii</span> species complex from the Amazonas State in Brazil" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "40" "paginaFinal" => "43" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Babbyngttonn Khell Da Silva, Ana Karla Freire, Amaury Dos Santos Bentes, Ivanete De Lima Sampaio, Lucilaide Oliveira Santos, Mirlane Silva Dos Santos, João Vicente De Souza" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Babbyngttonn" "apellidos" => "Khell Da Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Ana Karla" "apellidos" => "Freire" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Amaury" "apellidos" => "Dos Santos Bentes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Ivanete" "apellidos" => "De Lima Sampaio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Lucilaide" "apellidos" => "Oliveira Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Mirlane" "apellidos" => "Silva Dos Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:4 [ "nombre" => "João Vicente" "apellidos" => "De Souza" "email" => array:1 [ 0 => "joaovicentebragasouza@yahoo.com.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Fundação de Medicina Tropical do Amazonas, Manaus, AM, Brazil" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Nacional de Pesquisas da Amazônia, Manaus, AM, Brazil" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Caracterización de aislamientos clínicos del complejo <span class="elsevierStyleItalic">Cryptococcus neoformans-Cryptococcus gattii</span>, del Estado Amazonas - Brasil" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cryptococcosis is an opportunistic fungal disease caused by the encapsulated yeast species <span class="elsevierStyleItalic">Cryptococcus neoformans</span> and <span class="elsevierStyleItalic">Cryptococcus gattii</span>.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The infection is acquired by the inhalation of desiccated yeasts or spores and can develop to the brain or other systemic organs.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Infection with <span class="elsevierStyleItalic">Cryptococcus</span> spp. is the major cause of fungal meningitis in immunocompromised patients, resulting in elevated morbidity and mortality rates.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Furthermore, immunocompromised status is the most common risk factor for infection with <span class="elsevierStyleItalic">C. neoformans</span>. Additionally, there are increasing numbers of immunocompetent patients with fungal meningitis who are infected with <span class="elsevierStyleItalic">C. gattii</span>.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21,32</span></a> The preferred treatment for cryptococcal meningitis is amphotericin B, but a side effect of the drug manifested by nephrotoxicity limits its clinical use and increases the importance of antifungal susceptibility testing.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,12</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Based on serological studies, using antibodies against the fungal capsule, seven serotypes of <span class="elsevierStyleItalic">Cryptococcus</span> have been identified: A, B, C, D, AB, AD and BD.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,5,20</span></a><span class="elsevierStyleItalic">C. neoformans</span> serotypes A, D and AD are found in cities, whereas the <span class="elsevierStyleItalic">C. gattii</span> serotypes B and C are predominately localised in tropical and subtropical regions.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,13,19</span></a> In 1999 an outbreak of <span class="elsevierStyleItalic">C. gattii</span> occurred in Canada, raising the possibility that this species could be localised in both tropical and temperate climates.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In addition to the serotypes of <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gatti</span>, molecular analyses, including M13 fingerprinting, <span class="elsevierStyleItalic">URA5</span>-RFLP (Restriction Fragment Length Polymorphism) and AFLP (Amplified Fragment Length Polymorphism), have identified 8 molecular genotypes: VNI and VNII (Serotype A); VNIII (Hybrid AD); VNIV (Serotype D); and VGI, VGII, VGIII and VGIV (Serotypes B and C).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Molecular genotyping contributes to better and more accurate clinical diagnoses and characterizes genetic diversity for global epidemiological studies.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this work was to characterize forty <span class="elsevierStyleItalic">Cryptococcus</span> isolates from patients at the Tropical Medicine Foundation of Amazonas (FMTAM) during 2006–2008 by using phenotypic and molecular biological experiments.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1.1</span><span class="elsevierStyleSectionTitle">Isolates and strains</span><p id="par0025" class="elsevierStylePara elsevierViewall">Forty isolates were obtained from patients with cryptococcal infection who were hospitalized in FMTAM between March 2006 and February 2008. A single sample was collected from each patient and stored at 4<span class="elsevierStyleHsp" style=""></span>°C in the FMTAM fungal collection. They were grown on Sabouraud agar at 30<span class="elsevierStyleHsp" style=""></span>°C for 48<span class="elsevierStyleHsp" style=""></span>h. For molecular genotyping, the following standard strains were used: WM 148 (serotype A,VNI), WM 626 (serotype A, VNII), WM 628 (serotype AD, VNIII), WM 629 (serotype D, VNIV), WM 179 (serotype B, VGI), WM 178 (serotype B, VGII), WM 161 (serotype B, VGIII) and WM 779 (serotype C, VGIV). These reference strains were kindly provided by the fungal collection at FIOCRUZ-Rio de Janeiro-Brazil. Also, the reference strains WM 148 and WM 178 were used as reference strains for <span class="elsevierStyleSmallCaps">l</span>-canavanine glycine bromothymol blue (CGB) species determination, enzyme production and susceptibility assays using antifungal agents.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1.2</span><span class="elsevierStyleSectionTitle">Patient information</span><p id="par0030" class="elsevierStylePara elsevierViewall">The epidemiological profile of the patients (age, sex, immunological status and residence) was obtained by analysis of the examination requisition.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1.3</span><span class="elsevierStyleSectionTitle">Identification of the species</span><p id="par0035" class="elsevierStylePara elsevierViewall">CGB agar was utilized to differentiate the species <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span> as previously described.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleItalic">C. gattii</span> strains use the glycine in the media as a source of carbon and nitrogen, are resistant to canavanine and produce a blue cobalt colour during incubation, whereas <span class="elsevierStyleItalic">C. neoformans</span> do not exhibit any colour change in the media.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1.4</span><span class="elsevierStyleSectionTitle">Enzyme quantification</span><p id="par0040" class="elsevierStylePara elsevierViewall">The production of proteinases and phospholipases were measured as previously described.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23,25,33</span></a> The fungal isolates were inoculated at equidistant points on plates of proteinase agar and phospholipase agar, and the enzyme activity (Pz) was calculated using the relation between the diameter of the colony (dc) and the diameter of the colony and precipitation zone (dcp). The results were classified as negative (Pz<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1), positive (0.64<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>Pz<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1) or strongly positive (Pz<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.64).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1.5</span><span class="elsevierStyleSectionTitle">Susceptibility to antifungal agents</span><p id="par0045" class="elsevierStylePara elsevierViewall">Susceptibility tests were performed according to the Clinical and Laboratory Standards Institute (CLSI) document M44-A.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Disks impregnated with fluconazole (25<span class="elsevierStyleHsp" style=""></span>μg), itraconazole (10<span class="elsevierStyleHsp" style=""></span>μg) or amphotericin B (100<span class="elsevierStyleHsp" style=""></span>μg) (Cecon-Sensifungidisc, São Paulo, Brazil) were used in the assays. The diameter of the inhibition haloes was used to determine the susceptibility of the yeast to the antifungal compounds. Cut-off values were as follows: Amphotericin B<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mm – susceptible (S), <10<span class="elsevierStyleHsp" style=""></span>mm –resistant (R); itraconazol >20<span class="elsevierStyleHsp" style=""></span>mm – S, 19–12<span class="elsevierStyleHsp" style=""></span>mm – intermediate (I), <1<span class="elsevierStyleHsp" style=""></span>mm – R and fluconazole >19<span class="elsevierStyleHsp" style=""></span>mm – S; 19–14<span class="elsevierStyleHsp" style=""></span>mm – I; <14<span class="elsevierStyleHsp" style=""></span>mm – R. The determination of the MIC for amphotericin B was performed using the <span class="elsevierStyleItalic">E</span>-test-AB BIODISK method as described previously.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1.6</span><span class="elsevierStyleSectionTitle">Characterization of molecular genotypes</span><p id="par0050" class="elsevierStylePara elsevierViewall">The genotypic characterization was carried out as described previously.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Fungal DNA was extracted with the QIAamp tissue kit (Qiagen, Germany) according to the manufacturer's protocol for DNA extraction from yeast, including digestion with lyticase and RNAase. PCR of the <span class="elsevierStyleItalic">URA5</span> gene was conducted in a final volume of 50<span class="elsevierStyleHsp" style=""></span>μL, and each reaction contained 50<span class="elsevierStyleHsp" style=""></span>ng of DNA, 1× PCR buffer (10<span class="elsevierStyleHsp" style=""></span>mM Tris–HCl, pH 8.3, 50<span class="elsevierStyleHsp" style=""></span>mM KCl and 1.5<span class="elsevierStyleHsp" style=""></span>mM MgCl<span class="elsevierStyleInf">2</span>); 0.2<span class="elsevierStyleHsp" style=""></span>mM each of dATP, dCTP, dGTP and dTTP; 3<span class="elsevierStyleHsp" style=""></span>mM magnesium acetate; 1.5<span class="elsevierStyleHsp" style=""></span>U AmpliTaq DNA polymerase (Invitrogen, Carlsbad, California) and 50<span class="elsevierStyleHsp" style=""></span>ng of each primer <span class="elsevierStyleItalic">URA5</span> (5′ATGTCCTCCCAAGCCCTCGACTCCG3′) and SJ01 (5′TTAAGACCTCTGAACACCGTACTC3′). The PCR was performed in a PerkinElmer thermal cycler (model 480) for 35 cycles of a 2<span class="elsevierStyleHsp" style=""></span>min initial denaturation at 94<span class="elsevierStyleHsp" style=""></span>°C, 45<span class="elsevierStyleHsp" style=""></span>s denaturation at 94<span class="elsevierStyleHsp" style=""></span>°C, 1<span class="elsevierStyleHsp" style=""></span>min annealing at 61<span class="elsevierStyleHsp" style=""></span>°C and 2<span class="elsevierStyleHsp" style=""></span>min extension at 72<span class="elsevierStyleHsp" style=""></span>°C, followed by a final extension cycle for 10<span class="elsevierStyleHsp" style=""></span>min at 72<span class="elsevierStyleHsp" style=""></span>°C. The PCR products were double digested with <span class="elsevierStyleItalic">Sau</span>96I (10<span class="elsevierStyleHsp" style=""></span>U/μL) and <span class="elsevierStyleItalic">Hha</span>I (20<span class="elsevierStyleHsp" style=""></span>U/μL) for 3<span class="elsevierStyleHsp" style=""></span>h or overnight and separated by 3% agarose gel electrophoresis at 100<span class="elsevierStyleHsp" style=""></span>V for 5<span class="elsevierStyleHsp" style=""></span>h.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">The epidemiological characteristics of the patients with cryptococcosis were evaluated. Males were more commonly infected (70%) than females, and the age group most affected was between 16 and 30 years (53%; median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>28.5 years) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The majority of patients with cryptococcosis were also infected with HIV (72%) and resided in the east zone of the city of Manaus (25%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Cerebrospinal fluid (CSF) was collected for the isolation of the fungal agents from most patients (93%). Isolates were inoculated on a CGB medium; 9 were positive for the presence of <span class="elsevierStyleItalic">C. gattii</span>, and 31 were positive for <span class="elsevierStyleItalic">C. neoformans</span>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">All of the isolates had high protease production (Pz<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.64) and an average Pz<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.3 for both <span class="elsevierStyleItalic">Cryptococcus</span> species. All but 1 isolate was positive for the production of phospholipase (average Pz<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.53). Twenty-six <span class="elsevierStyleItalic">C. neoformans</span> isolates (83.8%) presented strong positive results (Pz<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.64), and 4 isolates (12.9%) presented positive results (Pz<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>0.64 and < 1.0), whereas all 9 isolates of <span class="elsevierStyleItalic">C. gattii</span> were classified as strong-positive producers of phospholipase.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Using the disk diffusion test (CLSI M44-A), 81, 35 and 100% of the isolates of <span class="elsevierStyleItalic">C. neoformans</span> were identified as susceptible to fluconazole, itraconazole and amphotericin B, respectively, and 78%, 56% and 100% of the isolates of <span class="elsevierStyleItalic">C. gattii</span> were susceptible to these antifungal compounds (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The average MIC for amphotericin B, evaluated by <span class="elsevierStyleItalic">E</span>-test methodology, was 0.26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.22<span class="elsevierStyleHsp" style=""></span>μg/mL for <span class="elsevierStyleItalic">C. neoformans</span> and 0.58<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.53<span class="elsevierStyleHsp" style=""></span>μg/mL for <span class="elsevierStyleItalic">C. gattii</span>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">DNA was extracted from all clinical isolates and was used to identify the molecular genotypes by <span class="elsevierStyleItalic">URA5</span>-RFLP. All 9 isolates of <span class="elsevierStyleItalic">C. gattii</span> possessed a fingerprint pattern consistent with the VGII molecular genotype, and all 31 isolates of <span class="elsevierStyleItalic">C. neoformans</span> had the profile of the VNI molecular type.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The total number of the inhabitants in the state of Amazonas is approximately 3.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span> and according to the Mycology Service of the Foundation of Tropical Medicine of Manaus, 20–25 new cases of cryptococcosis occur annually in the region. Manaus, the capital of Amazonas State, is located near the centre of the Amazon Basin on the left bank of the Rio Negro, consisting of Tertiary sediments on sandy-clay land. The region has an average rainfall of 2300<span class="elsevierStyleHsp" style=""></span>mm/year and is thus associated with a hot and humid climate and lush vegetation.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> In this study, the incidence of cryptococcosis was not related to these weather patterns, as the number of isolates was similar throughout the year. The identification of potential environmental sources of <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gatii</span> that are introduced into the human population requires further investigation. It is hypothesise that the sources of contamination are similar to those described in other countries: human infection with the <span class="elsevierStyleItalic">Cryptoccocus</span> type VNI primarily occurs from contact with bird faeces, and infection with the VGII type usually occurs following contact with decomposing vegetal biomass.</p><p id="par0080" class="elsevierStylePara elsevierViewall">This is one of the first studies to characterise cryptococcosis in the Amazonas State in Brazil. This study determined that the patients most affected by cryptococcosis were male, young (16–30 years old), HIV-positive and inhabitants of the east zone of the city of Manaus.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The number of cases of HIV/AIDS reported annually in the Amazonas State is approximately 700, half of them receive HAART treatment.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> AIDS is the most important risk factor for cryptococcosis, due to the suppression of immune responses by the HIV virus.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,13,26</span></a><span class="elsevierStyleItalic">C. neoformans</span> was the species most frequently isolated (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>31; 77.5%), which is consistent with the 82.3% reported in the literature.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,19</span></a><span class="elsevierStyleItalic">C. neoformans</span> almost exclusively causes disease in immunocompromised patients, and the majority of the isolates that we obtained came from patients with AIDS.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,19</span></a> Among the nine <span class="elsevierStyleItalic">C. gattii</span> isolates, three were obtained from immunocompetent patients, four from AIDS patients and two from patients without documented immune status.</p><p id="par0090" class="elsevierStylePara elsevierViewall">In this study, we obtained three isolates from children aged 0–15 years. <span class="elsevierStyleItalic">C. gattii</span> was the primary causative agent of meningitis in these patients. In a previous study in the Amazonas State from 1988 to 1998, Martins<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> reported that the frequency of cryptococcosis in children represented 33% of the total cases. In the Pará state, neighbouring the Amazonas State, 19–24% of cryptococcosis cases were reported in children over the last 10 years.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28,29</span></a> These studies demonstrate that in the Amazon Rainforest, the prevalence of cryptococcosis in children is high and is also associated with the molecular type VGII. Further epidemiological studies and environmental sampling are necessary to define the importance of the environmental conditions in the incidence of cryptococcosis cases in children.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The production of lipases and proteases is related to the virulence of <span class="elsevierStyleItalic">Cryptococcus</span> pathogenic species.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> These enzymes are involved in the destruction of cellular structures to both obtain nutrients for the fungal pathogens and to facilitate spread throughout tissues. Both <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span> produced proteases and lipases in similar quantities, and no difference was observed between molecular types.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Antifungal cryptococcosis testing showed 80% and 77% susceptibility to fluconazole in <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span>, respectively. This maintenance drug is commonly used in patients with AIDS to prevent opportunistic fungal diseases, and the emergence of resistant strains has been described.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,9</span></a><span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span> had 35% and 55% susceptibility to itraconozole, respectively, and all of the clinical isolates were susceptible to amphotericin B. These results are consistent with previous studies.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,22,27</span></a> Amphotericin B is considered to be the gold standard for cryptococcosis treatment.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In one study, amphotericin B resistance was reported in 10% of clinical isolates,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> but other studies demonstrate low in vitro resistance to this compound.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,27</span></a> Although all isolates were considered to be susceptible to amphotericin B (MIC<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>μg/mL), the average MIC of the <span class="elsevierStyleItalic">C. gattii</span> isolates (0.56<span class="elsevierStyleHsp" style=""></span>μg/mL) was greater than that of <span class="elsevierStyleItalic">C. neoformans</span> isolates (0.26<span class="elsevierStyleHsp" style=""></span>μg/mL). This result has been previously reported<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and highlights the potential for differential efficacy of therapeutics in the treatment of <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span>.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The identification of pathogenic <span class="elsevierStyleItalic">Cryptococcus</span> species and sub-species are important for both clinical guiding and as well as for epidemiology. Recently, false-positive <span class="elsevierStyleItalic">C. gattii</span> results have been reported using the conventional CGB differentiation method due to the existence of <span class="elsevierStyleItalic">C. neoformans</span> isolates that are resistant to canavanine<span class="elsevierStyleItalic">.</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Meanwhile, PCR fingerprinting and PCR-RFLP are being utilized more frequently.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,20,24</span></a> In the current study, PCR-RFLP was used to characterize the <span class="elsevierStyleItalic">Cryptococcus</span> isolates as the molecular types VNI and VGII. Furthermore, these results are consistent with previous studies that identified <span class="elsevierStyleItalic">C. neoformans</span> VNI as the primary agent of cryptococcosis.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,16,19</span></a> A study that characterized 63 Brazilian isolates described the prevalence of the molecular types VNI (82.3%), VGII (13.6%) and VNII (3.0%),<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and more recent studies in the Pará state reinforce the prevalence of VNI and VGII as being the principal molecular types of <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span>, respectively, in the northern region of Brazil.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Data from this study can assist with current and future management of cryptococcosis in Northern Brazil by identifying the frequency of <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span> in patients as well as their susceptibility to commonly used antifungal drugs. These data also contribute to epidemiological studies of the distribution of different molecular types of <span class="elsevierStyleItalic">Cryptococcus</span> species in the Brazilian Amazon.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres121165" "titulo" => array:6 [ 0 => "Abstract" 1 => "Background" 2 => "Aims" 3 => "Methods" 4 => "Results" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec108451" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres121166" "titulo" => array:6 [ 0 => "Resumen" 1 => "Antecedentes" 2 => "Objetivos" 3 => "Métodos" 4 => "Resultados" 5 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec108452" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Isolates and strains" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patient information" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Identification of the species" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Enzyme quantification" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Susceptibility to antifungal agents" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Characterization of molecular genotypes" ] ] ] 5 => array:2 [ "identificador" => "sec0045" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 8 => array:2 [ "identificador" => "xack37740" "titulo" => "Acknowledgement" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-08-09" "fechaAceptado" => "2011-05-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec108451" "palabras" => array:4 [ 0 => "<span class="elsevierStyleItalic">Cryptococcus neoformans</span>" 1 => "<span class="elsevierStyleItalic">Cryptococcus gattii</span>" 2 => "Epidemiology" 3 => "Phenotyping and genotyping" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec108452" "palabras" => array:4 [ 0 => "<span class="elsevierStyleItalic">Cryptococcus neoformans</span>" 1 => "<span class="elsevierStyleItalic">Cryptococcus gattii</span>" 2 => "Epidemiología" 3 => "Fenotipo y genotipo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The differentiation and classification of pathogenic <span class="elsevierStyleItalic">Cryptococcus</span> species provides useful data for epidemiological studies and for the clinical diagnosis and treatment of patients.</p> <span class="elsevierStyleSectionTitle">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to characterise 40 clinical <span class="elsevierStyleItalic">Cryptococcus</span> isolates obtained from patients at the Tropical Medicine Foundation of Amazonas (FMTAM) from 2006 to 2008.</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">It was used phenotypic (i.e., enzyme production and antifungal resistance) and molecular biological (<span class="elsevierStyleItalic">URA5</span>-RFLP) experiments.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patients with HIV/AIDS were most affected with cryptococcosis. Thirty-one (75.5%) of the clinical isolates were classified as <span class="elsevierStyleItalic">Cryptococcus neoformans</span> and 9 (22.5%) as <span class="elsevierStyleItalic">Cryptococcus gattii</span>. High amounts of protease and phospholipase enzymes were produced by most of the isolates. Using the disk diffusion test (CLSI M44-A), 81, 35 and 100% of the <span class="elsevierStyleItalic">C. neoformans</span> isolates were characterized as susceptible to fluconazole, itraconazole and amphotericin B, respectively, whereas 78, 56 and 100% of the <span class="elsevierStyleItalic">C. gattii</span> isolates were susceptible to these antimicrobial agents. The average of Minimal Inhibitory Concentration (MIC) for <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span> isolates was 0.26 and 0.58<span class="elsevierStyleHsp" style=""></span>μg/mL, respectively. The 9 isolates of <span class="elsevierStyleItalic">C. gattii</span> had a fingerprint pattern comparable with the VGII molecular type, while all 31 isolates of <span class="elsevierStyleItalic">C. neoformans</span> presented with a pattern consistent with the VNI type.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">This study confirms the importance of HIV/AIDS for the cryptococcosis epidemiology, the susceptibility of the isolates to amphotericin B and the high prevalence of the molecular genotypes VNI and VGII in the north of Brazil.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La diferenciación y clasificación de las especies patógenas del género <span class="elsevierStyleItalic">Cryptococcus</span> aporta datos importantes para la asistencia clínica y para estudios epidemiológicos.</p> <span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este trabajo fue caracterizar 40 aislamientos clínicos del complejo <span class="elsevierStyleItalic">Cryptococcus neoformans</span> de pacientes que fueron atendidos en la Fundación de Medicina Tropical de Amazonas desde 2006 hasta 2008.</p> <span class="elsevierStyleSectionTitle">Métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se utilizaron métodos fenotípicos (producción de enzimas y pruebas de sensibilidad a los antifúngicos) y moleculares (URA5-RFLP).</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con VIH/sida fueron los más afectados de criptococosis. Se observó que 31 (75,5%) y 9 (22,5%) de los aislamientos fueron <span class="elsevierStyleItalic">Cryptococcus neoformans</span> y <span class="elsevierStyleItalic">Cryptococcus gattii</span>, respectivamente. La producción de proteasa y fosfolipasa fue alta en la mayoría de las cepas. Utilizando la prueba de difusión en disco (CLSI M44-A) se observó que el 81, 35 y 100% de los aislamientos de <span class="elsevierStyleItalic">C. neoformans</span> fueron sensibles al fluconazol, itraconazol y amphotericin B, respectivamente, mientras que 78, 56 y 100% de los aislamientos de <span class="elsevierStyleItalic">C. gattii</span> fueron sensibles a estas sustancias. El valor promedio de la concentración mínima inhibitoria (CMI) para <span class="elsevierStyleItalic">C. neoformans</span> y <span class="elsevierStyleItalic">C. gattii</span> fue de 0,26 y 0,58<span class="elsevierStyleHsp" style=""></span>mg/ml, respectivamente. Todos los aislamientos (9) de <span class="elsevierStyleItalic">C. gattii</span> presentaron un patrón de electroforesis compatible con el genotipo VGII, y todos los aislamientos (31) de <span class="elsevierStyleItalic">C. neoformans</span> presentaron el genotipo VNI.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Este estudio confirma la importancia del HIV/sida para la epidemiología de la criptococosis, la sensibilidad de los aislamientos a la anfotericina B y la alta prevalencia de los genotipos moleculares VNI y VGII en el norte de Brasil.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">C. neoformans</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">C. gattii</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Total (%) \t\t\t\t\t\t\n \t\t\t\t</td></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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Sex</span> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (30) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (70) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age (Years)</span> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0– 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (8) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>16–30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (53) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>31–45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (25) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>46–60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>>60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">HIV Infection</span> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (73) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (18) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Area of the residence in Manaus</span> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>North \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>South \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (8) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>East \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (24) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>West \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>South Central \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (8) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Midwest \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (33) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Biological sample</span> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cerebrospinal fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (92) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Blood culture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5) \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="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sputum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab209030.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Epidemiological characteristics of patients with cryptococcosis.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antifungal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Susceptible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Intermediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Resistant \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-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">N (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">N (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">N (%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">C. neoformans</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluconazole \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">25 (80.6) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">5 (16.1) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.3) \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="\n \t\t\t\t\ttop\n \t\t\t\t">Itraconazole \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">11 (35.4) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">20 (64.6) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \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="\n \t\t\t\t\ttop\n \t\t\t\t">Amphotericin B \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">31 (100) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">C. gattii</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluconazole \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">7 (77.7) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">2 (22.3) \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="\n \t\t\t\t\ttop\n \t\t\t\t">Itraconazole \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">5 (55.5) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">4 (44.5) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \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="\n \t\t\t\t\ttop\n \t\t\t\t">Amphotericin B \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">9 (100) \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\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="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab209029.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">- Susceptibility of <span class="elsevierStyleItalic">C. neoformans</span> and <span class="elsevierStyleItalic">C. gattii</span> to antifungal compounds, as measured by disk diffusion.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Urban sources of <span class="elsevierStyleItalic">Cryptococcus spp</span> – Lisbon" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.M. Bernardo" 1 => "H.M. Martins" 2 => "M.L. Martins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ver Port Clin" "fecha" => "2001" "volumen" => "96" "paginaInicial" => "157" "paginaFinal" => "160" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Brasil, Ministério da Saúde. Documentos e publicações em DST e AIDS. Coordenação do programa nacional de DTS/AIDS. <span class="elsevierStyleItalic">Epidemiol Vigilance</span>. 2004:1. 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De Bedout" 1 => "N. Ordóñez" 2 => "B.L. Gómez" 3 => "M.C. Rodríguez" 4 => "M. Arango" 5 => "A. Restrepo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Iberoam Micol" "fecha" => "1999" "volumen" => "16" "paginaInicial" => "36" "paginaFinal" => "39" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18473590" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of three commercial assays and a modified disk diffusion assay with two broth microdilution reference assays for testing zygomycetes, <span class="elsevierStyleItalic">Aspergillus</span> spp., <span class="elsevierStyleItalic">Candida</span> spp., and <span class="elsevierStyleItalic">Cryptococcus neoformans</span> with posaconazole and amphotericin B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Espinel-Ingroff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.01187-06" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "3616" "paginaFinal" => "3622" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16943356" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of inositol phospho-sphingolipid-phospholipase C1 (Isc1) in <span class="elsevierStyleItalic">Cryptococcus neoformans</span> reveals unique biochemical features" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Henry" 1 => "A. Guillotte" 2 => "C. Luberto" 3 => "M. 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2023 August | 4 | 7 | 11 |
2023 July | 8 | 10 | 18 |
2023 June | 5 | 5 | 10 |
2023 May | 7 | 11 | 18 |
2023 April | 5 | 7 | 12 |
2023 March | 7 | 5 | 12 |
2023 February | 9 | 11 | 20 |
2023 January | 27 | 11 | 38 |
2022 December | 15 | 5 | 20 |
2022 November | 17 | 17 | 34 |
2022 October | 21 | 10 | 31 |
2022 September | 9 | 8 | 17 |
2022 August | 9 | 12 | 21 |
2022 July | 8 | 9 | 17 |
2022 June | 10 | 11 | 21 |
2022 May | 22 | 3 | 25 |
2022 April | 17 | 24 | 41 |
2022 March | 19 | 10 | 29 |
2022 February | 6 | 11 | 17 |
2022 January | 8 | 11 | 19 |
2021 December | 11 | 11 | 22 |
2021 November | 12 | 9 | 21 |
2021 October | 6 | 4 | 10 |
2021 September | 11 | 15 | 26 |
2021 August | 9 | 6 | 15 |
2021 July | 6 | 6 | 12 |
2021 June | 9 | 8 | 17 |
2021 May | 8 | 7 | 15 |
2021 April | 15 | 18 | 33 |
2021 March | 17 | 9 | 26 |
2021 February | 7 | 11 | 18 |
2021 January | 9 | 16 | 25 |
2020 December | 12 | 8 | 20 |
2020 November | 8 | 7 | 15 |
2020 October | 7 | 10 | 17 |
2020 September | 9 | 13 | 22 |
2020 August | 14 | 12 | 26 |
2020 July | 5 | 4 | 9 |
2020 June | 9 | 8 | 17 |
2020 May | 10 | 12 | 22 |
2020 April | 5 | 10 | 15 |
2020 March | 9 | 9 | 18 |
2020 February | 3 | 4 | 7 |
2020 January | 10 | 11 | 21 |
2019 December | 7 | 4 | 11 |
2019 November | 6 | 16 | 22 |
2019 October | 4 | 3 | 7 |
2019 September | 4 | 8 | 12 |
2019 August | 7 | 5 | 12 |
2019 July | 15 | 11 | 26 |
2019 June | 23 | 19 | 42 |
2019 May | 50 | 15 | 65 |
2019 April | 21 | 23 | 44 |
2019 March | 1 | 5 | 6 |
2019 February | 4 | 4 | 8 |
2019 January | 3 | 6 | 9 |
2018 December | 3 | 2 | 5 |
2018 November | 9 | 4 | 13 |
2018 October | 3 | 4 | 7 |
2018 September | 18 | 5 | 23 |
2018 August | 2 | 6 | 8 |
2018 July | 5 | 5 | 10 |
2018 June | 2 | 0 | 2 |
2018 May | 3 | 9 | 12 |
2018 April | 8 | 0 | 8 |
2018 March | 9 | 4 | 13 |
2018 February | 13 | 0 | 13 |
2018 January | 4 | 2 | 6 |
2017 December | 19 | 2 | 21 |
2017 November | 3 | 3 | 6 |
2017 October | 11 | 3 | 14 |
2017 September | 9 | 5 | 14 |
2017 August | 20 | 28 | 48 |
2017 July | 7 | 4 | 11 |
2017 June | 17 | 27 | 44 |
2017 May | 17 | 13 | 30 |
2017 April | 12 | 20 | 32 |
2017 March | 10 | 7 | 17 |
2017 February | 10 | 3 | 13 |
2017 January | 21 | 4 | 25 |
2016 December | 24 | 10 | 34 |
2016 November | 13 | 9 | 22 |
2016 October | 50 | 2 | 52 |
2016 September | 17 | 7 | 24 |
2016 August | 22 | 5 | 27 |
2016 July | 17 | 3 | 20 |
2016 June | 42 | 10 | 52 |
2016 May | 32 | 6 | 38 |
2016 April | 9 | 7 | 16 |
2016 March | 4 | 5 | 9 |
2016 February | 9 | 4 | 13 |
2016 January | 21 | 8 | 29 |
2015 December | 29 | 5 | 34 |
2015 November | 31 | 3 | 34 |
2015 October | 27 | 5 | 32 |
2015 September | 34 | 6 | 40 |
2015 August | 38 | 2 | 40 |
2015 July | 25 | 5 | 30 |
2015 June | 35 | 1 | 36 |
2015 May | 27 | 5 | 32 |
2015 April | 13 | 3 | 16 |
2015 March | 32 | 4 | 36 |
2015 February | 27 | 2 | 29 |
2015 January | 28 | 3 | 31 |
2014 December | 42 | 6 | 48 |
2014 November | 39 | 1 | 40 |
2014 October | 42 | 6 | 48 |
2014 September | 41 | 2 | 43 |
2014 August | 45 | 0 | 45 |
2014 July | 35 | 0 | 35 |
2014 June | 38 | 2 | 40 |
2014 May | 27 | 3 | 30 |
2014 April | 27 | 2 | 29 |
2014 March | 44 | 8 | 52 |
2014 February | 45 | 17 | 62 |
2014 January | 40 | 8 | 48 |
2013 December | 56 | 5 | 61 |
2013 November | 36 | 14 | 50 |
2013 October | 15 | 16 | 31 |
2013 September | 17 | 10 | 27 |
2013 August | 31 | 7 | 38 |
2013 July | 24 | 8 | 32 |
2013 June | 12 | 5 | 17 |
2013 May | 15 | 9 | 24 |
2013 April | 19 | 10 | 29 |
2013 March | 13 | 11 | 24 |
2013 February | 8 | 4 | 12 |
2013 January | 7 | 6 | 13 |
2012 December | 4 | 3 | 7 |
2012 November | 2 | 2 | 4 |
2012 October | 2 | 1 | 3 |
2012 January | 778 | 0 | 778 |