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compared to other transmissible infectious diseases&#44; it still is a considerable social&#44; health care and economic burden and remains a top health priority&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Invasive meningococcal disease typically manifests with acute sepsis and&#47;or meningitis that may result in death within a few hours&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> In Spain&#44; despite adequate treatment&#44; its associated mortality is 10&#37;&#44; and 10&#37;&#8211;20&#37; of survivors experience sequelae&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Invasive meningococcal disease poses a challenge to clinicians due to the difficulty of early diagnosis in some patients and to the complexity of the care required by the most severe cases&#46; The initial signs and symptoms are often nonspecific&#44; especially in infants&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a> which complicates differential diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">11&#44;12</span></a> Early administration of antibiotics and initiation of life support are the cornerstones of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">7&#44;13&#44;14</span></a> In IMD&#44; early identification of patients at risk of having a poor outcome from the first contact with primary care is of vital importance&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> as early treatment and transfer to intensive care is associated with increased survival and a decreased incidence of sequelae&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a> To this end&#44; several predictors of severity have been proposed&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of our study was to explore the epidemiology and clinical characteristics of IMD in the paediatric population of Navarra in the age of universal vaccination against meningococcus C&#44; and to identify the clinical and laboratory findings at diagnosis that are associated with a poor prognosis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We conducted a retrospective study between 2008 and 2014&#44; a period in which the routine immunisation against meningococcus C was well established that we considered to be long enough to reflect the current situation of IMD&#46; The population under study included every child aged less than 15 years residing in Navarra&#44; which amounted to approximately 95<span class="elsevierStyleHsp" style=""></span>500 inhabitants&#46; We defined a case as any patient aged less than 15 years with clinical manifestations compatible with IMD and with microbiological confirmation of <span class="elsevierStyleItalic">N&#46; meningitidis</span> in blood or cerebrospinal fluid &#40;CSF&#41; samples &#40;isolation in culture&#44; DNA detection by polymerase chain reaction&#44; or antigen detection by immunoassay&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We obtained the epidemiological and microbiological data of all cases from the active IMD surveillance system records included in the Register of Notifiable Diseases of Navarra&#46; We completed this information with data from medical records in 46 cases&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We calculated the incidence of IMD using the population size recorded in the census on January 1 for each age group and year as the denominator&#44; using data from the Instituto Nacional de Estad&#237;stica &#40;National Institute of Statistics&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We defined sepsis&#44; septic shock&#44; severe sepsis and organ dysfunction based on the criteria of the 2005 International Consensus Conference on Pediatric Sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> We classified patients that did not meet the criteria for sepsis but in whom viable bacteria were isolated from blood as cases of bacteraemia&#46; We took into account clinical signs of shock following the Spanish Clinical Practice Guideline on the Management of Invasive Meningococcal Disease<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> &#40;unusual skin colour&#44; peripheral coldness&#44; capillary refill time &#62;2<span class="elsevierStyleHsp" style=""></span>s&#44; mental confusion or decreased level of consciousness&#44; tachycardia or hypotension&#44; respiratory difficulty or pain in the extremities&#41;&#46; We defined disseminated intravascular coagulation &#40;DIC&#41; as the presence of laboratory findings characteristic of this pathology&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">We defined poor outcome as the presence of permanent sequelae &#40;present 3 months after discharge&#41; or death&#46; The factors analysed for a potential association with poor outcome were&#58; duration of symptoms before arrival to hospital &#40;&#60;12&#59; 12&#8211;23 and &#8805;24<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; manifestations of sepsis in the absence of meningitis&#44; skin lesions either extensive &#40;generalised or disseminated&#44; found in the trunk and extremities&#41; or advanced &#40;purpura or ecchymosis&#41;&#44; a score of less than 15 in the Glasgow coma scale&#44; one or more episodes of seizures&#44; clinical criteria of severe sepsis&#44; leukopaenia &#40;leucocytes &#60;4500&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; neutropaenia &#40;neutrophils &#60;900&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; thrombocytopaenia &#40;platelets &#60;150<span class="elsevierStyleHsp" style=""></span>000&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; product of platelet and neutrophil counts &#40;PN product&#41; of less than 40&#215;10<span class="elsevierStyleSup">9</span>&#47;L&#44; base excess &#40;BE&#41; of less than &#8722;8&#44; procalcitonin &#40;PCT&#41; greater than 100<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; and DIC&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">All the cases received inpatient care in the public health care network of Navarra&#44; which consists of one tertiary referral hospital and two regional hospitals&#46; To assess prognostic factors&#44; we analysed the values recorded at the time of admission in any of the hospitals &#40;initial history-taking&#44; physical examination and blood work&#41;&#44; except for DIC&#44; for which we took into account the presence of clinical criteria at any point during the episode of disease&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">To analyse the factors associated with a poor prognosis&#44; we conducted a bivariate analysis comparing each clinical or laboratory finding &#40;independent variable&#41; and poor outcome &#40;dependent variable&#41;&#46; This analysis included the 46 cases for which we had access to medical records&#46; We performed the comparisons with Fisher&#39;s exact test&#46; We defined statistical significance as a <span class="elsevierStyleItalic">p</span>-value of less than &#46;05&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Epidemiology</span><p id="par0065" class="elsevierStylePara elsevierViewall">The study included a total of 53 cases of IMD between 2008 and 2014&#46; The incidence of IMD showed a predominantly decreasing trend &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The mean annual incidence was 7&#46;9 cases per 100<span class="elsevierStyleHsp" style=""></span>000 individuals&#46; Cases occurred predominantly in the winter months &#40;weeks 1&#8211;4 and 45&#8211;53&#41;&#46; We found no statistically significant differences between sexes &#40;58&#37; male&#44; 42&#37; female&#41;&#46; The mean age of the patients was 2&#46;7 years &#40;standard deviation &#91;SD&#93;&#44; 4&#46;5 years&#41;&#44; and 83&#37; of the children were aged less than 5 years&#46; The annual incidence was highest in children aged less than one year &#40;40&#46;7 cases per 100<span class="elsevierStyleHsp" style=""></span>000&#41;&#44; followed by children aged 1&#8211;4 years &#40;13&#46;3 cases per 100<span class="elsevierStyleHsp" style=""></span>000&#41; and children aged 5&#8211;14 years &#40;2&#46;1 cases per 100<span class="elsevierStyleHsp" style=""></span>000&#41;&#46; In 87&#37; of patients&#44; the isolate was of the B serogroup&#44; in 4&#37; of the C serogroup and in 2&#37; of the Y serogroup&#46; Eight percent of cases were caused by nontypeable meningococci&#46; Ninety-three percent of patients with IMD had been vaccinated with the MenC vaccine&#46; Of the two cases with group C meningococcus&#44; one was due to vaccination failure &#40;the patient was correctly vaccinated for age&#41; and the other occurred in a child whose parents had refused vaccination&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clinical and laboratory findings at diagnosis</span><p id="par0070" class="elsevierStylePara elsevierViewall">The most frequent clinical presentation was combined sepsis&#8211;meningitis &#40;36&#37;&#41;&#44; followed by sepsis &#40;34&#37;&#41;&#44; meningitis &#40;17&#37;&#41; and bacteraemia &#40;13&#37;&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The mean time elapsed between the onset of symptoms and seeking care was 23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3<span class="elsevierStyleHsp" style=""></span>h&#46; Twenty-two percent sought care in the first 12<span class="elsevierStyleHsp" style=""></span>h&#44; forty-eight percent 12&#8211;23<span class="elsevierStyleHsp" style=""></span>h after onset&#44; and thirty percent at 24<span class="elsevierStyleHsp" style=""></span>h or more&#46; Eighty-one percent of patients presenting with sepsis or sepsis&#8211;meningitis sought care in the first 24<span class="elsevierStyleHsp" style=""></span>h compared to forty-three percent of the patients that presented with meningitis or bacteraemia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;026&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The signs and symptoms present most frequently at diagnosis were fever&#44; exanthem &#40;haemorrhagic in most cases&#41; and signs of shock &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Meningeal signs were negative in 48&#37; of the patients in which meningitis or sepsis&#8211;meningitis was subsequently confirmed&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">The complete blood count detected leukocytosis in 82&#37; of patients&#44; neutrophilia in 60&#37; and thrombocytopaenia in 11&#37;&#46; Procalcitonin was elevated in 94&#37; of patients in whom it was measured&#44; and C reactive protein was elevated in 53&#37;&#46; Measurement of pH detected metabolic acidosis in 70&#37; of cases &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Treatment and outcome</span><p id="par0090" class="elsevierStylePara elsevierViewall">All patients with IMD were admitted to the inpatient paediatric ward and 68&#37; were also admitted to the paediatric intensive care unit &#40;PICU&#41; &#40;100&#37; of sepsis&#8211;meningitis&#44; 67&#37; of sepsis and 56&#37; of meningitis cases&#41;&#46; The mean total length of stay was 12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;8 days&#44; while the mean stay in the PICU was 6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;2 days&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The most frequent type of organ dysfunction was cardiovascular &#40;60&#37;&#41;&#44; followed by haematological &#40;58&#37;&#41;&#44; respiratory &#40;42&#37;&#41;&#44; neurologic &#40;36&#37;&#41; and renal &#40;9&#37;&#41;&#46; No patient developed liver dysfunction&#46; Thirteen percent of patients developed DIC and one third had multiple organ dysfunction&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">All the patients received intravenous antibiotherapy &#40;98&#37; cefotaxime and 2&#37; ceftriaxone&#41;&#46; Some patients also required volume expanders &#40;69&#37;&#41;&#44; vasoactive and inotropic agents &#40;67&#37;&#41;&#44; oxygen therapy &#40;65&#37;&#41;&#44; corticosteroids &#40;42&#37;&#41;&#44; intubation &#40;10&#37;&#41; or transfusion of blood products &#40;9&#37;&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Condition at discharge</span><p id="par0105" class="elsevierStylePara elsevierViewall">Two patients aged 10 and 12 months died&#44; resulting in a mortality of 3&#46;8&#37; and a mean annual mortality of 0&#46;3 deaths per 100<span class="elsevierStyleHsp" style=""></span>000 individuals &#40;2&#46;1 deaths per 100<span class="elsevierStyleHsp" style=""></span>000 children &#60;2 years&#41;&#46; The two deaths occurred in patients with multiple organ failure secondary to septic shock that did not respond to treatment&#46; The isolated strain was from serogroup B in one of these patients and nontypeable in the other&#46; In both cases&#44; death occurred within 12<span class="elsevierStyleHsp" style=""></span>h from the onset of symptoms&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Of the 51 patients that survived&#44; 24&#37; experienced some sort of sequela &#40;sepsis group&#44; 39&#37;&#59; sepsis&#8211;meningitis group&#44; 32&#37;&#59; and meningitis group&#44; 11&#37;&#41;&#44; and the sequelae were permanent in 10&#37;&#46; The most frequent temporary sequelae were due to soft tissue necrosis&#46; The permanent sequelae were deafness &#40;40&#37;&#41;&#44; limb amputation &#40;40&#37;&#41; and other neurologic impairment &#40;20&#37;&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Signs associated with poor outcome</span><p id="par0115" class="elsevierStylePara elsevierViewall">A score of less than 15 in the Glasgow Coma Scale &#40;odds ratio &#91;OR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;2&#41;&#44; having at least one seizure &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#46;3&#41;&#44; clinical manifestations of sepsis in the absence of meningitis &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;1&#41;&#44; thrombocytopaenia &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#46;5&#41; and DIC &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#46;9&#41; were significantly associated with poor outcome &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46; The association for extensive or advanced skin lesions did not reach statistical significance&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">We found a decreasing incidence of IMD in Navarra between 2008 and 2014&#44; as has been documented for the rest of Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> The increased incidence in winter<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> and the greater burden of disease in young children are consistent with the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">1&#44;2</span></a> As is the case in other Western countries&#44; we found a significant predominance of serogroup B&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> The low incidence of cases caused by serogroup B is associated with the high vaccination coverage with the MenC vaccine in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The most frequent clinical presentation was sepsis&#44; but in the literature there is variation in the most predominant form&#8212;sepsis or meningitis&#8212;from study to study&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">11&#44;21</span></a> Patients presenting with sepsis and sepsis&#8211;meningitis sought care before patients with other forms of disease&#44; probably on account of the rapid progression and severity of these cases&#46; Fever and exanthem&#44; which are symptoms frequently described in cases of IMD&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15&#44;21&#44;22</span></a> were the manifestations found most frequently at the time of diagnosis&#46; The exanthem was not haemorrhagic in two out of ten patients&#44; which is a relevant finding&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> as less serious infections in children often present with non-haemorrhagic exanthem&#46; Consistent with other studies&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a> a considerable proportion of patients presented with some sign of shock on arrival to the hospital&#46; This fact is worth noting&#44; as some of these signs manifest in the early stages<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> and knowing how to recognise them is important for the purpose of early diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">11&#44;12</span></a> Meningeal signs were negative in almost one out of every two patients presenting with sepsis&#8211;meningitis or meningitis&#44; possibly because they manifest at a later time or because they often do not develop in infants&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">7&#44;11</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The abnormal laboratory findings were consistent with the previous literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15&#44;23</span></a> The proportion of patients with elevated PCT was higher than the proportion with elevated C-reactive protein&#46; This may be related to the rapid progression of most cases and supports the hypothesis that due to its earlier elevation&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> PCT is more useful in the diagnosis of meningococcal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In IMD&#44; there is a massive activation of the inflammatory cascade and the coagulation pathway&#44; which causes damage to the internal organs of the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> The severity of this disease is evinced by the percentage of patients admitted to the PICU and the need for life support measures&#46; Our findings are consistent with those of other authors as to lethality&#44; mortality and mean length of stay&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">6</span></a> with most deaths occurring in the first 24<span class="elsevierStyleHsp" style=""></span>h&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">11&#44;21</span></a> and the frequency and type of sequelae&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Many studies have analysed clinical and laboratory markers&#44; alone or in the form of scales&#44; as potential prognostic factors in IMD&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">16&#44;26&#8211;32</span></a> In our study&#44; sepsis without meningitis&#44; seizure&#44; and a score of less than 15 in the Glasgow Coma Scale were the clinical factors with the highest predictive value for a poor outcome&#46; We did not find an association between the duration of symptoms and poor outcome&#44; probably because the most severe cases tend to seek care earlier and counteract a worse initial prognosis with earlier initiation of care&#46; The association with the presence of extensive or advanced exanthem was not statistically significant&#44; but is nevertheless considered relevant in prognostication&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">7&#44;30&#44;33</span></a> Thrombocytopaenia and DIC were the laboratory parameters that best predicted a poor outcome&#46; This is a relevant finding&#44; as the platelet count is an accessible and economic test with a demonstrated predictive value<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a> that is used in various composite scales&#44; such as the PN product&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Protocols for the management of paediatric patients with IMD can incorporate thrombocytopaenia as a marker for poor prognosis&#44; one that could be particularly useful in facilities in which more sophisticated tests for other markers are not available&#46; Children with thrombocytopaenia or other abnormal laboratory findings compatible with DIC&#44; as well as children presenting with sepsis but not meningitis&#44; a score of less than 15 in the Glasgow Coma Scale or that experience seizures should be considered at high risk&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The findings of this study must be interpreted taking its limitations into account&#46; Although our study included all cases of IMD in Navarra&#44; the sample size was small and restricted to a specific geographical area&#46; The retrospective design may have led to biases&#46; We did not consider whether patients with IMD had previously visited their primary care clinic or collect data for other symptoms such as headache&#44; vomiting or photophobia&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15&#44;21</span></a> We were unable to obtain the laboratory values for all the patients&#46; In some cases that resulted in permanent sequelae or death&#44; the PCT&#44; BE and leukocytecountin CSF were not available&#44; so the association of these parameters with a poor outcome may be stronger than found in our analysis&#46; Furthermore&#44; in most cases&#44; BE was measured in samples of venous blood&#44; and the presence of DIC&#44; which was documented at more advanced stages&#44; may have been given more weight than other factors&#46; We did not analyse psychological sequelae&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The recent introduction in the market of the meningococcal B vaccine in Spain marks the dawn of a new era in the prevention of IMD&#46; This new development will probably lead to changes in this disease in the near future&#44; so the situation that we have described may serve as the starting point for new studies evaluating the impact of the new vaccine in coming years&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">To conclude&#44; despite the significant advances made in the prevention of IMD with the routine immunisation of children against serogroup C meningococcus&#44; the disease continues to be a significant health problem in the paediatric age group&#46; The early recognition of symptoms&#44; the optimisation of initial treatment in emergency care settings and the urgent transfer of patients to facilities with a PICU are key strategies to reducing mortality and the incidence of sequelae in children with IMD&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec817002"
          "palabras" => array:5 [
            0 => "Enfermedad meningoc&#243;cica"
            1 => "Epidemiolog&#237;a"
            2 => "Caracter&#237;sticas cl&#237;nicas"
            3 => "Factores pron&#243;sticos"
            4 => "Vacuna conjugada"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systematic childhood vaccination against meningococcus C has had a considerable impact on meningococcal invasive disease &#40;MID&#41;&#46; The aim of this study is to perform an analysis on the epidemiology&#44; the clinical features&#44; and the factors associated with a worse prognosis of MID&#44; in the era of a meningococcal C vaccine&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The study included confirmed cases of MID in children less than 15 years of age in Navarra&#44; Spain&#44; between 2008 and 2014&#46; The risk of death or permanent sequelae was evaluated according to the presence of clinical features and analytical parameters at diagnosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The average annual incidence was 7&#46;9 cases per 100<span class="elsevierStyleHsp" style=""></span>000 children&#44; with the highest attack rate in children &#60;1 year&#46; Of 53 cases analysed&#44; 87&#37; were due to meningococcus B&#46; Fever &#40;100&#37;&#41;&#44; rash &#40;91&#37;&#41;&#44; and elevation of procalcitonin &#40;94&#37;&#41; were the most frequent findings at diagnosis&#46; Some sign of shock was observed in 70&#37; upon arrival at the hospital&#46; The case-fatality rate was 3&#46;8&#37; and 10&#37; survived with permanent sequelae&#46; Glasgow coma scale &#60;15 &#40;odds ratio &#91;OR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;2&#41;&#44; seizure &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#46;3&#41;&#44; sepsis without meningitis &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;1&#41;&#44; thrombocytopenia &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#46;5&#41;&#44; and disseminated intravascular coagulation &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#46;9&#41; showed a greater association with a worse prognosis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The MID continues to be a significant cause of morbidity and mortality in children&#46; Therefore&#44; new advances are needed in the prevention&#44; early diagnosis&#44; and detection of the factors associated with poor prognosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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            "identificador" => "abst0010"
            "titulo" => "Material and methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La vacunaci&#243;n sistem&#225;tica infantil frente al meningococo C ha tenido un impacto considerable en la enfermedad meningoc&#243;cica invasiva &#40;EMI&#41;&#46; El objetivo de este estudio es analizar la epidemiolog&#237;a&#44; las manifestaciones cl&#237;nicas y los factores asociados a un peor pron&#243;stico de la EMI en la era de la vacuna antimeningoc&#243;cica C&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se analizaron los casos de EMI confirmados en menores de 15 a&#241;os diagnosticados en Navarra entre 2008 y 2014&#44; y se evalu&#243; el riesgo de muerte o secuelas permanentes&#44; seg&#250;n la presencia de determinados hallazgos cl&#237;nicos o anal&#237;ticos al diagn&#243;stico&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La incidencia media anual fue 7&#44;9 casos por 100&#46;000 ni&#241;os&#44; con mayor tasa de ataque en ni&#241;os &#60; 1 a&#241;o&#46; De 53 casos analizados&#44; el 87&#37; fueron por meningococo B&#46; Fiebre &#40;100&#37;&#41;&#44; exantema &#40;91&#37;&#41; y elevaci&#243;n de la procalcitonina &#40;94&#37;&#41; fueron los hallazgos m&#225;s frecuentes al diagn&#243;stico&#46; El 70&#37; de los casos presentaba alg&#250;n signo de shock a su llegada al hospital&#46; La letalidad fue del 3&#44;8&#37; y un 10&#37; sobrevivi&#243; con secuelas permanentes&#46; Una puntuaci&#243;n en la escala de coma de Glasgow &#60; 15 &#40;odds ratio &#91;OR&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#44;2&#41;&#44; convulsi&#243;n &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44;3&#41;&#44; sepsis sin meningitis &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#44;1&#41;&#44; trombocitopenia &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#44;5&#41; y coagulaci&#243;n intravascular diseminada &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#44;9&#41; se asociaron con un peor pron&#243;stico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La EMI contin&#250;a causando una morbimortalidad importante en la poblaci&#243;n infantil&#44; por lo que sigue siendo necesario avanzar en su prevenci&#243;n&#44; en su diagn&#243;stico temprano y en reconocer los factores asociados a mal pron&#243;stico&#46;</p></span>"
        "secciones" => array:4 [
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            "titulo" => "Introducci&#243;n"
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            "titulo" => "Material y m&#233;todos"
          ]
          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="npar0015">Please cite this article as&#58; Morales D&#44; Moreno L&#44; Herranz M&#44; Bernaola E&#44; Mart&#237;nez-Baz I&#44; Castilla J&#46; Enfermedad meningoc&#243;cica invasiva en Navarra en la era de la vacuna conjugada antimeningoc&#243;cica C&#46; An Pediatr &#40;Barc&#41;&#46; 2017&#59;86&#58;213&#8211;219&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Incidence of invasive meningococcal disease in children aged less than 15 years in Navarra&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">One patient died on admission to hospital&#44; so no laboratory data were available&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Procalcitonin level measurement started in year 2009&#46;</p>"
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                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" style="border-bottom: 2px solid black">Clinical manifestations&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">Total <span class="elsevierStyleItalic">N</span>&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">Frequency<br><span class="elsevierStyleItalic">N</span> &#40;&#37;&#41;&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Axillary temperature &#8805;38</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#176;C</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Axillary temperature &#8805;39<span class="elsevierStyleHsp" style=""></span>&#176;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&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;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Exanthem</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&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;91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Haemorrhagic exanthem&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;72&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Signs of shock</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Glasgow Coma Scale score &#60;15</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Seizure</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;13&#41;&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="3" 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="3" align="left" valign="top"><span class="elsevierStyleItalic">Blood test values</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Procalcitonin &#62;0&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&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;94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Leucocytes &#62;10<span class="elsevierStyleHsp" style=""></span>000&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&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;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Base excess &#60;&#8722;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&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;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polymorphonuclear leukocytes &#62;70&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C-reactive protein &#62;10<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&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;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Platelets &#60;150<span class="elsevierStyleHsp" style=""></span>000&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Leucocytes &#60;4500&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Neutrophils &#60;900&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Clinical and laboratory findings at diagnosis in patients with invasive meningococcal disease aged less than 15 years in Navarra&#44; 2008&#8211;2014&#46;</p>"
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                  <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" style="border-bottom: 2px solid black">Clinical factors&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">Total <span class="elsevierStyleItalic">N</span>&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">Poor outcome<br><span class="elsevierStyleItalic">N</span> &#40;&#37;&#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">Crude odds ratio &#40;95&#37; confidence interval&#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"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Sepsis without meningitis</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;6&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;38&#46;5&#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;1 &#40;1&#46;5&#8211;78&#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">&#46;015&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Severe sepsis</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;20&#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">4&#46;1 &#40;0&#46;5&#8211;102&#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">&#46;209&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Extensive&#47;advanced skin lesions</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;4&#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">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;26&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;5 &#40;1&#46;0&#8211;187&#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">&#46;053&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Glasgow Coma Scale score &#60;15</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;4&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;28&#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">9&#46;2 &#40;1&#46;2&#8211;230&#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">&#46;030&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Time elapsed between onset of symptoms to seeking care</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#60;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;10&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>12&#8211;23<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#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">2&#46;0 &#40;0&#46;2&#8211;4&#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">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8805;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;14&#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">1&#46;5 &#40;0&#46;1&#8211;19&#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">1&#46;000&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Seizures</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;10&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;50&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;3 &#40;1&#46;1&#8211;65&#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">&#46;040&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <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" style="border-bottom: 2px solid black">Laboratory parameters &#40;tested in blood&#44; except the last&#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">Total <span class="elsevierStyleItalic">N</span>&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">Poor outcome<br><span class="elsevierStyleItalic">N</span> &#40;&#37;&#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">Crude odds ratio &#40;95&#37; confidence interval&#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"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Leucocytes &#60;4500&#47;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;12&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;3 &#40;0&#46;1&#8211;27&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;528&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Neutrophils &#60;900&#47;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;11&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;33&#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">3&#46;6 &#40;0&#46;1&#8211;54&#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">&#46;399&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Platelets &#60;150</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">000&#47;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;66&#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">30&#46;5 &#40;3&#46;6&#8211;377&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;001&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Procalcitonin &#62;100</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ng&#47;mL</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#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">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;40&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#46;7 &#40;0&#46;9&#8211;526&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;068&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Disseminated intravascular coagulation</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;50&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;5 &#40;0&#46;1&#8211;206&#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">&#46;400&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;133&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Leucocytesin cerebrospinal fluid &#60;10&#47;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;10&#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">1&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#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 &#40;0&#46;0&#8211;34&#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">&#46;808&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Laboratory findings associated with poor outcome in patients with invasive meningococcal disease aged less than 15 years in Navarra&#44; 2008&#8211;2014&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global epidemiology of meningococcal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;H&#46; Harrison"
                            1 => "C&#46;L&#46; Trotter"
                            2 => "M&#46;E&#46; Ramsay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.vaccine.2009.04.063"
                      "Revista" => array:7 [
                        "tituloSerie" => "Vaccine"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "numero" => "Suppl&#46; 2"
                        "paginaInicial" => "B51"
                        "paginaFinal" => "B63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19477562"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Meningococcal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "N&#46;E&#46; Rosenstein"
                            1 => "B&#46;A&#46; Perkins"
                            2 => "D&#46;S&#46; Stephens"
                            3 => "T&#46; Popovic"
                            4 => "J&#46;M&#46; Hughes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM200105033441807"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "344"
                        "paginaInicial" => "1378"
                        "paginaFinal" => "1388"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11333996"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemic meningitis&#44; meningococcaemia&#44; and <span class="elsevierStyleItalic">Neisseria meningitidis</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;S&#46; Stephens"
                            1 => "B&#46; Greenwood"
                            2 => "P&#46; Brandtzaeg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(07)61016-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2007"
                        "volumen" => "369"
                        "paginaInicial" => "2196"
                        "paginaFinal" => "2210"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17604802"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0185"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "&#91;Invasive meningococcal disease&#93;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;A&#46; Soult Rubio"
                            1 => "M&#46; Munoz Saez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "An Pediatr &#40;Barc&#41;"
                        "fecha" => "2005"
                        "volumen" => "62"
                        "paginaInicial" => "297"
                        "paginaFinal" => "303"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Red Nacional de Vigilancia Epidemiol&#243;gica&#46; Enfermedad meningoc&#243;cica en Espa&#241;a&#46; An&#225;lisis de la temporada 2012&#8211;2013&#46; Available from <a href="http://www.isciii.es/ISCIII/es/contenidos/fd-servicios-cientifico-tecnicos/fd-vigilancias-alertas/fd-enfermedades/MNG_informe_2012-2013_confirmados.pdf">http&#58;&#47;&#47;www&#46;isciii&#46;es&#47;ISCIII&#47;es&#47;contenidos&#47;fd-servicios-cientifico-tecnicos&#47;fd-vigilancias-alertas&#47;fd-enfermedades&#47;MNG&#95;informe&#95;2012-2013&#95;confirmados&#46;pdf</a> &#91;accessed 26&#46;07&#46;15&#93;"
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden of hospitalizations for meningococcal infection in Spain &#40;1997&#8211;2008&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Gil-Prieto"
                            1 => "L&#46; Garcia-Garcia"
                            2 => "A&#46; Alvaro-Meca"
                            3 => "A&#46; Gonzalez-Escalada"
                            4 => "P&#46; Viguera Ester"
                            5 => "A&#46; Gil de Miguel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.vaccine.2011.05.089"
                      "Revista" => array:6 [
                        "tituloSerie" => "Vaccine"
                        "fecha" => "2011"
                        "volumen" => "29"
                        "paginaInicial" => "5765"
                        "paginaFinal" => "5770"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21664402"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Grupo de trabajo de la Gu&#237;a de Pr&#225;ctica Cl&#237;nica sobre el Manejo de la Enfermedad Meningoc&#243;cica Invasiva&#46; Gu&#237;a de pr&#225;ctica cl&#237;nica sobre el manejo de la enfermedad meningoc&#243;cica invasiva&#46; Ministerio de Sanidad&#44; Servicios Sociales e Igualdad&#46; Instituto Aragon&#233;s de Ciencias de la Salud&#59; 2013&#46; Available from&#58; <a href="http://www.guiasalud.es/GPC/GPC_525_EMI_ICS_compl.pdf">http&#58;&#47;&#47;www&#46;guiasalud&#46;es&#47;GPC&#47;GPC&#95;525&#95;EMI&#95;ICS&#95;compl&#46;pdf</a> &#91;accessed 12&#46;10&#46;15&#93;"
                ]
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              "etiqueta" => "8"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of invasive meningococcal serogroup B disease in children and adolescents &#40;MOSAIC&#41;&#58; a case-control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;M&#46; Viner"
                            1 => "R&#46; Booy"
                            2 => "H&#46; Johnson"
                            3 => "W&#46;J&#46; Edmunds"
                            4 => "L&#46; Hudson"
                            5 => "H&#46; Bedford"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1474-4422(12)70180-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Neurol"
                        "fecha" => "2012"
                        "volumen" => "11"
                        "paginaInicial" => "774"
                        "paginaFinal" => "783"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22863608"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
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              "etiqueta" => "9"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Outcomes of invasive meningococcal disease in adults and children in Canada between 2002 and 2011&#58; a prospective cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Sadarangani"
                            1 => "D&#46;W&#46; Scheifele"
                            2 => "S&#46;A&#46; Halperin"
                            3 => "W&#46; Vaudry"
                            4 => "N&#46; le Saux"
                            5 => "R&#46; Tsang"
                          ]
                        ]
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                      "doi" => "10.1093/cid/civ028"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2015"
                        "volumen" => "60"
                        "paginaInicial" => "e27"
                        "paginaFinal" => "e35"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25605282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0215"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Clinical spectrum of meningococcal infection in infants younger than six months of age"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46;R&#46; Huang"
                            1 => "H&#46;L&#46; Chen"
                            2 => "S&#46;M&#46; Chu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chang Gung Med J"
                        "fecha" => "2006"
                        "volumen" => "29"
                        "paginaInicial" => "107"
                        "paginaFinal" => "113"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16642734"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0220"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical recognition of meningococcal disease in children and adolescents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;J&#46; Thompson"
                            1 => "N&#46; Ninis"
                            2 => "R&#46; Perera"
                            3 => "R&#46; Mayon-White"
                            4 => "C&#46; Phillips"
                            5 => "L&#46; Bailey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(06)67932-4"
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                        "tituloSerie" => "Lancet"
                        "fecha" => "2006"
                        "volumen" => "367"
                        "paginaInicial" => "397"
                        "paginaFinal" => "403"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16458763"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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                    0 => array:2 [
                      "titulo" => "Which early &#8220;red flag&#8221; symptoms identify children with meningococcal disease in primary care"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;A&#46; Haj-Hassan"
                            1 => "M&#46;J&#46; Thompson"
                            2 => "R&#46;T&#46; Mayn-White"
                            3 => "N&#46; Ninis"
                            4 => "A&#46; Harnden"
                            5 => "L&#46;F&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3399/bjgp11X561131"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Gen Pract"
                        "fecha" => "2011"
                        "volumen" => "61"
                        "paginaInicial" => "e97"
                        "paginaFinal" => "e104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21375891"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "National Institute for Health and Clinical Excellence&#46; Bacterial meningitis and meningococcal septicaemia&#46; Management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care&#46; NICE clinical guideline 1023 National Collaborating Centre for Women&#39;s and Children&#39;s Health&#59; 2010&#46; Available from&#58; <a href="http://www.nice.org.uk/nicemedia/live/13027/49339/49339.pdf">http&#58;&#47;&#47;www&#46;nice&#46;org&#46;uk&#47;nicemedia&#47;live&#47;13027&#47;49339&#47;49339&#46;pdf</a> &#91;accessed 08&#46;10&#46;15&#93;"
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Alonso Salas MT&#44; De Carlos Vicente JC&#44; Gil Ant&#243;n J&#44; Pinto Fuentes I&#44; Quintilla Martinez JM&#44; S&#225;nchez D&#237;az JI&#46; Documento de consenso SECIP-SEUP sobre manejo de sepsis grave y shock s&#233;ptico en pediatr&#237;a&#46; Available from&#58; <a href="http://www.seup.org/pdf_public/pub/consenso_sepsis_shock.pdf">http&#58;&#47;&#47;www&#46;seup&#46;org&#47;pdf&#95;public&#47;pub&#47;consenso&#95;sepsis&#95;shock&#46;pdf</a> &#91;accessed 10&#46;10&#46;15&#93;"
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis and management of meningococcal disease&#58; the need for centralized care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Nadel"
                            1 => "J&#46;S&#46; Kroll"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1574-6976.2006.00059.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "FEMS Microbiol Rev"
                        "fecha" => "2007"
                        "volumen" => "31"
                        "paginaInicial" => "71"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17233636"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic markers of meningococcal disease in children&#58; recent advances and future challenges"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Montero-Martin"
                            1 => "D&#46;P&#46; Inwald"
                            2 => "E&#46;D&#46; Carrol"
                            3 => "F&#46; Martinon-Torres"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Exp Rev Anti Infect Ther"
                        "fecha" => "2014"
                        "volumen" => "12"
                        "paginaInicial" => "1357"
                        "paginaFinal" => "1369"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International pediatric sepsis consensus conference&#58; definitions for sepsis and organ dysfunction in pediatrics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "B&#46; Goldstein"
                            1 => "B&#46; Giroir"
                            2 => "A&#46; Randolph"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.PCC.0000149131.72248.E6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "6"
                        "paginaInicial" => "2"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15636651"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disseminated intravascular coagulation current concepts of etiology&#44; pathophysiology&#44; diagnosis&#44; and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;L&#46; Bick"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hematol Oncol Clin North Am"
                        "fecha" => "2003"
                        "volumen" => "17"
                        "paginaInicial" => "149"
                        "paginaFinal" => "176"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12627667"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of infant meningococcal disease in the United States&#44; 2006&#8211;2012"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; MacNeil"
                            1 => "N&#46; Bennett"
                            2 => "M&#46;M&#46; Farley"
                            3 => "L&#46;H&#46; Harrison"
                            4 => "R&#46; Lynfield"
                            5 => "M&#46; Nichols"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1542/peds.2014-2035"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2015"
                        "volumen" => "135"
                        "paginaInicial" => "e305"
                        "paginaFinal" => "e311"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25583921"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changes in meningococcal C epidemiology and vaccine effectiveness after vaccine introduction and schedule modification"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Garrido-Estepa"
                            1 => "I&#46; Leon-Gomez"
                            2 => "R&#46; Herruzo"
                            3 => "R&#46; Cano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.vaccine.2014.03.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Vaccine"
                        "fecha" => "2014"
                        "volumen" => "32"
                        "paginaInicial" => "2604"
                        "paginaFinal" => "2609"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24662700"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical presentation of meningococcal disease in childhood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; Sabatini"
                            1 => "S&#46; Bosis"
                            2 => "M&#46; Semino"
                            3 => "L&#46; Senatore"
                            4 => "N&#46; Principi"
                            5 => "S&#46; Esposito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Prev Med Hyg"
                        "fecha" => "2012"
                        "volumen" => "53"
                        "paginaInicial" => "116"
                        "paginaFinal" => "119"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23240173"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic clinical and laboratory findings in response to predetermining bacterial pathogen&#58; data from the Meningitis Registry"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Karanika"
                            1 => "V&#46;A&#46; Vasilopoulou"
                            2 => "A&#46;T&#46; Katsioulis"
                            3 => "P&#46; Papastergiou"
                            4 => "M&#46;N&#46; Theodoridou"
                            5 => "C&#46;S&#46; Hadjichristodoulou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0006426"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2009"
                        "volumen" => "4"
                        "paginaInicial" => "e6426"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19641629"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated procalcitonin as a diagnostic marker in meningococcal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;D&#46; Mills"
                            1 => "H&#46;M&#46; Lala"
                            2 => "M&#46;R&#46; Oehley"
                            3 => "A&#46;B&#46; Craig"
                            4 => "K&#46; Barratt"
                            5 => "D&#46; Hood"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10096-006-0179-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Clin Microbiol Infect Dis"
                        "fecha" => "2006"
                        "volumen" => "25"
                        "paginaInicial" => "501"
                        "paginaFinal" => "509"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16896823"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Variation in serum C-reactive protein across the clinical spectrum of meningococcal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "O&#46; Maruk"
                            1 => "K&#46; Bestwick"
                            2 => "A&#46;P&#46; Thomson"
                            3 => "J&#46;A&#46; Sills"
                            4 => "C&#46;A&#46; Hart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "1993"
                        "volumen" => "82"
                        "paginaInicial" => "729"
                        "paginaFinal" => "733"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8241667"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46;D&#46; Carrol"
                            1 => "P&#46; Newland"
                            2 => "F&#46;A&#46; Riordan"
                            3 => "A&#46;P&#46; Thomson"
                            4 => "N&#46; Curtis"
                            5 => "C&#46;A&#46; Hart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dis Child"
                        "fecha" => "2002"
                        "volumen" => "86"
                        "paginaInicial" => "282"
                        "paginaFinal" => "285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11919107"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;D&#46; Carrol"
                            1 => "A&#46;P&#46; Thomson"
                            2 => "A&#46;P&#46; Jones"
                            3 => "G&#46; Jeffers"
                            4 => "C&#46;A&#46; Hart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-005-2787-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2005"
                        "volumen" => "31"
                        "paginaInicial" => "1415"
                        "paginaFinal" => "1419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16132884"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0300"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multivariable predictive models for adverse outcome of invasive meningococcal disease in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Malley"
                            1 => "W&#46;C&#46; Huskins"
                            2 => "N&#46; Kuppermann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "1996"
                        "volumen" => "129"
                        "paginaInicial" => "702"
                        "paginaFinal" => "710"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8917237"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Procalcitonin as a prognostic marker in meningococcal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D&#46;C&#46; Van der Kaay"
                            1 => "E&#46;D&#46; de Kleijn"
                            2 => "Y&#46;B&#46; de Rijke"
                            3 => "W&#46;C&#46; Hop"
                            4 => "R&#46; de Groot"
                            5 => "J&#46;A&#46; Hazelzet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-002-1505-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2002"
                        "volumen" => "28"
                        "paginaInicial" => "1606"
                        "paginaFinal" => "1612"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12415448"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0310"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early severe neutropenia and thrombocytopenia identifies the highest risk cases of severe meningococcal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;J&#46; Peters"
                            1 => "R&#46;I&#46; Ross-Russell"
                            2 => "D&#46; White"
                            3 => "S&#46;J&#46; Kerr"
                            4 => "F&#46;E&#46; Eaton"
                            5 => "I&#46;N&#46; Keengwe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Crit Care Med"
                        "fecha" => "2001"
                        "volumen" => "2"
                        "paginaInicial" => "225"
                        "paginaFinal" => "231"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12793946"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognosis of meningococcal septicaemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;F&#46; Sinclair"
                            1 => "C&#46;H&#46; Skeoch"
                            2 => "D&#46; Hallworth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2215-0366(14)00050-9"
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1987"
                        "volumen" => "2"
                        "paginaInicial" => "38"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26359611"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new prognostic scoring system for meningococcal septic shock in children&#46; Comparison with three other scoring systems"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Castellanos-Ortega"
                            1 => "M&#46; Delgado-Rodriguez"
                            2 => "J&#46; Llorca"
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Journal Information
Vol. 86. Issue 4.
Pages 213-219 (1 April 2017)
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5137
Vol. 86. Issue 4.
Pages 213-219 (1 April 2017)
Original Article
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Invasive meningococcal disease in Navarra in the era of a meningococcal C vaccine
Enfermedad meningocócica invasiva en Navarra en la era de la vacuna conjugada antimeningocócica C
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5137
Desirée Moralesa,
Corresponding author
, Laura Morenob,c, Mercedes Herranzb,c, Enrique Bernaolab,c, Iván Martínez-Bazc,d,e, Jesús Castillac,d,e
a Centro de Salud de Noáin, Noáin, Navarra, Spain
b Servicio de Pediatría, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain
c Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain
d Instituto de Salud Pública de Navarra, Pamplona, Navarra, Spain
e CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
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Figures (1)
Tables (3)
Table 1. Clinical and laboratory findings at diagnosis in patients with invasive meningococcal disease aged less than 15 years in Navarra, 2008–2014.
Table 2. Clinical factors associated with poor outcomes in patients with invasive meningococcal disease aged less than 15 years in Navarra, 2008–2014.
Table 3. Laboratory findings associated with poor outcome in patients with invasive meningococcal disease aged less than 15 years in Navarra, 2008–2014.
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Abstract
Introduction

Systematic childhood vaccination against meningococcus C has had a considerable impact on meningococcal invasive disease (MID). The aim of this study is to perform an analysis on the epidemiology, the clinical features, and the factors associated with a worse prognosis of MID, in the era of a meningococcal C vaccine.

Material and methods

The study included confirmed cases of MID in children less than 15 years of age in Navarra, Spain, between 2008 and 2014. The risk of death or permanent sequelae was evaluated according to the presence of clinical features and analytical parameters at diagnosis.

Results

The average annual incidence was 7.9 cases per 100000 children, with the highest attack rate in children <1 year. Of 53 cases analysed, 87% were due to meningococcus B. Fever (100%), rash (91%), and elevation of procalcitonin (94%) were the most frequent findings at diagnosis. Some sign of shock was observed in 70% upon arrival at the hospital. The case-fatality rate was 3.8% and 10% survived with permanent sequelae. Glasgow coma scale <15 (odds ratio [OR]=9.2), seizure (OR=8.3), sepsis without meningitis (OR=9.1), thrombocytopenia (OR=30.5), and disseminated intravascular coagulation (OR=10.9) showed a greater association with a worse prognosis.

Conclusion

The MID continues to be a significant cause of morbidity and mortality in children. Therefore, new advances are needed in the prevention, early diagnosis, and detection of the factors associated with poor prognosis.

Keywords:
Meningococcal disease
Epidemiology
Clinical features
Prognostic factors
Conjugate vaccine
Resumen
Introducción

La vacunación sistemática infantil frente al meningococo C ha tenido un impacto considerable en la enfermedad meningocócica invasiva (EMI). El objetivo de este estudio es analizar la epidemiología, las manifestaciones clínicas y los factores asociados a un peor pronóstico de la EMI en la era de la vacuna antimeningocócica C.

Material y métodos

Se analizaron los casos de EMI confirmados en menores de 15 años diagnosticados en Navarra entre 2008 y 2014, y se evaluó el riesgo de muerte o secuelas permanentes, según la presencia de determinados hallazgos clínicos o analíticos al diagnóstico.

Resultados

La incidencia media anual fue 7,9 casos por 100.000 niños, con mayor tasa de ataque en niños < 1 año. De 53 casos analizados, el 87% fueron por meningococo B. Fiebre (100%), exantema (91%) y elevación de la procalcitonina (94%) fueron los hallazgos más frecuentes al diagnóstico. El 70% de los casos presentaba algún signo de shock a su llegada al hospital. La letalidad fue del 3,8% y un 10% sobrevivió con secuelas permanentes. Una puntuación en la escala de coma de Glasgow < 15 (odds ratio [OR]=9,2), convulsión (OR=8,3), sepsis sin meningitis (OR=9,1), trombocitopenia (OR=30,5) y coagulación intravascular diseminada (OR=10,9) se asociaron con un peor pronóstico.

Conclusión

La EMI continúa causando una morbimortalidad importante en la población infantil, por lo que sigue siendo necesario avanzar en su prevención, en su diagnóstico temprano y en reconocer los factores asociados a mal pronóstico.

Palabras clave:
Enfermedad meningocócica
Epidemiología
Características clínicas
Factores pronósticos
Vacuna conjugada
Full Text
Introduction

Invasive meningococcal disease (IMD), caused by the bacterium Neisseria meningitidis (N. meningitidis, known as meningococcus), is a severe infection that primarily affects young children.1–4

In Spain, the inclusion of the conjugate vaccine against group C meningococcus (MenC) in the routine immunisation schedule in 2001 was followed by a decline in the incidence of IMD, which was down to approximately 0.8 cases per 100000 inhabitants per year by 2012–2013.5 However, compared to other transmissible infectious diseases, it still is a considerable social, health care and economic burden and remains a top health priority.6,7

Invasive meningococcal disease typically manifests with acute sepsis and/or meningitis that may result in death within a few hours.2 In Spain, despite adequate treatment, its associated mortality is 10%, and 10%–20% of survivors experience sequelae.8,9

Invasive meningococcal disease poses a challenge to clinicians due to the difficulty of early diagnosis in some patients and to the complexity of the care required by the most severe cases. The initial signs and symptoms are often nonspecific, especially in infants,10 which complicates differential diagnosis.11,12 Early administration of antibiotics and initiation of life support are the cornerstones of treatment.7,13,14 In IMD, early identification of patients at risk of having a poor outcome from the first contact with primary care is of vital importance,12 as early treatment and transfer to intensive care is associated with increased survival and a decreased incidence of sequelae.15 To this end, several predictors of severity have been proposed.16

The aim of our study was to explore the epidemiology and clinical characteristics of IMD in the paediatric population of Navarra in the age of universal vaccination against meningococcus C, and to identify the clinical and laboratory findings at diagnosis that are associated with a poor prognosis.

Materials and methods

We conducted a retrospective study between 2008 and 2014, a period in which the routine immunisation against meningococcus C was well established that we considered to be long enough to reflect the current situation of IMD. The population under study included every child aged less than 15 years residing in Navarra, which amounted to approximately 95500 inhabitants. We defined a case as any patient aged less than 15 years with clinical manifestations compatible with IMD and with microbiological confirmation of N. meningitidis in blood or cerebrospinal fluid (CSF) samples (isolation in culture, DNA detection by polymerase chain reaction, or antigen detection by immunoassay).

We obtained the epidemiological and microbiological data of all cases from the active IMD surveillance system records included in the Register of Notifiable Diseases of Navarra. We completed this information with data from medical records in 46 cases.

We calculated the incidence of IMD using the population size recorded in the census on January 1 for each age group and year as the denominator, using data from the Instituto Nacional de Estadística (National Institute of Statistics).

We defined sepsis, septic shock, severe sepsis and organ dysfunction based on the criteria of the 2005 International Consensus Conference on Pediatric Sepsis.17 We classified patients that did not meet the criteria for sepsis but in whom viable bacteria were isolated from blood as cases of bacteraemia. We took into account clinical signs of shock following the Spanish Clinical Practice Guideline on the Management of Invasive Meningococcal Disease7 (unusual skin colour, peripheral coldness, capillary refill time >2s, mental confusion or decreased level of consciousness, tachycardia or hypotension, respiratory difficulty or pain in the extremities). We defined disseminated intravascular coagulation (DIC) as the presence of laboratory findings characteristic of this pathology.18

We defined poor outcome as the presence of permanent sequelae (present 3 months after discharge) or death. The factors analysed for a potential association with poor outcome were: duration of symptoms before arrival to hospital (<12; 12–23 and ≥24h), manifestations of sepsis in the absence of meningitis, skin lesions either extensive (generalised or disseminated, found in the trunk and extremities) or advanced (purpura or ecchymosis), a score of less than 15 in the Glasgow coma scale, one or more episodes of seizures, clinical criteria of severe sepsis, leukopaenia (leucocytes <4500/mm3), neutropaenia (neutrophils <900/mm3), thrombocytopaenia (platelets <150000/mm3), product of platelet and neutrophil counts (PN product) of less than 40×109/L, base excess (BE) of less than −8, procalcitonin (PCT) greater than 100ng/mL, and DIC.

All the cases received inpatient care in the public health care network of Navarra, which consists of one tertiary referral hospital and two regional hospitals. To assess prognostic factors, we analysed the values recorded at the time of admission in any of the hospitals (initial history-taking, physical examination and blood work), except for DIC, for which we took into account the presence of clinical criteria at any point during the episode of disease.

To analyse the factors associated with a poor prognosis, we conducted a bivariate analysis comparing each clinical or laboratory finding (independent variable) and poor outcome (dependent variable). This analysis included the 46 cases for which we had access to medical records. We performed the comparisons with Fisher's exact test. We defined statistical significance as a p-value of less than .05.

ResultsEpidemiology

The study included a total of 53 cases of IMD between 2008 and 2014. The incidence of IMD showed a predominantly decreasing trend (Fig. 1). The mean annual incidence was 7.9 cases per 100000 individuals. Cases occurred predominantly in the winter months (weeks 1–4 and 45–53). We found no statistically significant differences between sexes (58% male, 42% female). The mean age of the patients was 2.7 years (standard deviation [SD], 4.5 years), and 83% of the children were aged less than 5 years. The annual incidence was highest in children aged less than one year (40.7 cases per 100000), followed by children aged 1–4 years (13.3 cases per 100000) and children aged 5–14 years (2.1 cases per 100000). In 87% of patients, the isolate was of the B serogroup, in 4% of the C serogroup and in 2% of the Y serogroup. Eight percent of cases were caused by nontypeable meningococci. Ninety-three percent of patients with IMD had been vaccinated with the MenC vaccine. Of the two cases with group C meningococcus, one was due to vaccination failure (the patient was correctly vaccinated for age) and the other occurred in a child whose parents had refused vaccination.

Figure 1.

Incidence of invasive meningococcal disease in children aged less than 15 years in Navarra.

(0.1MB).
Clinical and laboratory findings at diagnosis

The most frequent clinical presentation was combined sepsis–meningitis (36%), followed by sepsis (34%), meningitis (17%) and bacteraemia (13%).

The mean time elapsed between the onset of symptoms and seeking care was 23±6.3h. Twenty-two percent sought care in the first 12h, forty-eight percent 12–23h after onset, and thirty percent at 24h or more. Eighty-one percent of patients presenting with sepsis or sepsis–meningitis sought care in the first 24h compared to forty-three percent of the patients that presented with meningitis or bacteraemia (p=.026).

The signs and symptoms present most frequently at diagnosis were fever, exanthem (haemorrhagic in most cases) and signs of shock (Table 1). Meningeal signs were negative in 48% of the patients in which meningitis or sepsis–meningitis was subsequently confirmed.

Table 1.

Clinical and laboratory findings at diagnosis in patients with invasive meningococcal disease aged less than 15 years in Navarra, 2008–2014.

Clinical manifestations  Total N  Frequency
N (%) 
Axillary temperature ≥38°C  46  46 (100) 
Axillary temperature ≥39°C  46  35 (76) 
Exanthem  46  42 (91) 
Haemorrhagic exanthem  46  33 (72) 
Signs of shock  46  32 (70) 
Glasgow Coma Scale score <15  46  21 (46) 
Seizure  46  6 (13) 
Blood test values
Procalcitonin >0.5ng/mL  32  30 (94) 
Leucocytes >10000/mm3  45  37 (82) 
Base excess <−2  20  14 (70) 
Polymorphonuclear leukocytes >70%  45  27 (60) 
C-reactive protein >10mg/dL  45  25 (53) 
Platelets <150000/mm3  45  5 (11) 
Leucocytes <4500/mm3  45  4 (9) 
Neutrophils <900/mm3  45  3 (7) 

One patient died on admission to hospital, so no laboratory data were available.

Procalcitonin level measurement started in year 2009.

The complete blood count detected leukocytosis in 82% of patients, neutrophilia in 60% and thrombocytopaenia in 11%. Procalcitonin was elevated in 94% of patients in whom it was measured, and C reactive protein was elevated in 53%. Measurement of pH detected metabolic acidosis in 70% of cases (Table 1).

Treatment and outcome

All patients with IMD were admitted to the inpatient paediatric ward and 68% were also admitted to the paediatric intensive care unit (PICU) (100% of sepsis–meningitis, 67% of sepsis and 56% of meningitis cases). The mean total length of stay was 12±9.8 days, while the mean stay in the PICU was 6±7.2 days.

The most frequent type of organ dysfunction was cardiovascular (60%), followed by haematological (58%), respiratory (42%), neurologic (36%) and renal (9%). No patient developed liver dysfunction. Thirteen percent of patients developed DIC and one third had multiple organ dysfunction.

All the patients received intravenous antibiotherapy (98% cefotaxime and 2% ceftriaxone). Some patients also required volume expanders (69%), vasoactive and inotropic agents (67%), oxygen therapy (65%), corticosteroids (42%), intubation (10%) or transfusion of blood products (9%).

Condition at discharge

Two patients aged 10 and 12 months died, resulting in a mortality of 3.8% and a mean annual mortality of 0.3 deaths per 100000 individuals (2.1 deaths per 100000 children <2 years). The two deaths occurred in patients with multiple organ failure secondary to septic shock that did not respond to treatment. The isolated strain was from serogroup B in one of these patients and nontypeable in the other. In both cases, death occurred within 12h from the onset of symptoms.

Of the 51 patients that survived, 24% experienced some sort of sequela (sepsis group, 39%; sepsis–meningitis group, 32%; and meningitis group, 11%), and the sequelae were permanent in 10%. The most frequent temporary sequelae were due to soft tissue necrosis. The permanent sequelae were deafness (40%), limb amputation (40%) and other neurologic impairment (20%).

Signs associated with poor outcome

A score of less than 15 in the Glasgow Coma Scale (odds ratio [OR]=9.2), having at least one seizure (OR=8.3), clinical manifestations of sepsis in the absence of meningitis (OR=9.1), thrombocytopaenia (OR=30.5) and DIC (OR=10.9) were significantly associated with poor outcome (Tables 2 and 3). The association for extensive or advanced skin lesions did not reach statistical significance.

Table 2.

Clinical factors associated with poor outcomes in patients with invasive meningococcal disease aged less than 15 years in Navarra, 2008–2014.

Clinical factors  Total N  Poor outcome
N (%) 
Crude odds ratio (95% confidence interval)  pa 
Sepsis without meningitis
No  33  2 (6.1)   
Yes  13  5 (38.5)  9.1 (1.5–78.2)  .015 
Severe sepsis
No  17  1 (5.9)   
Yes  29  6 (20.7)  4.1 (0.5–102.3)  .209 
Extensive/advanced skin lesions
No  23  1 (4.3)   
Yes  23  6 (26.1)  7.5 (1.0–187.2)  .053 
Glasgow Coma Scale score <15
No  25  1 (4.0)   
Yes  21  6 (28.6)  9.2 (1.2–230.6)  .030 
Time elapsed between onset of symptoms to seeking care
<1210  1 (10.0)   
12–2322  4 (18.2)  2.0 (0.2–4.6)  1.000 
≥2414  2 (14.3)  1.5 (0.1–19.2)  1.000 
Seizures
No  40  4 (10.0)   
Yes  3 (50.0)  8.3 (1.1–65.3)  .040 
a

p for a two-tailed Fisher's exact test.

Table 3.

Laboratory findings associated with poor outcome in patients with invasive meningococcal disease aged less than 15 years in Navarra, 2008–2014.

Laboratory parameters (tested in blood, except the last)  Total N  Poor outcome
N (%) 
Crude odds ratio (95% confidence interval)  pa 
Leucocytes <4500/mm3
No  41  5 (12.2)   
Yes  1 (25.0)  2.3 (0.1–27.0)  .528 
Neutrophils <900/mm3
No  42  5 (11.9)   
Yes  1 (33.3)  3.6 (0.1–54.4)  .399 
Platelets <150000/mm3
No  39  2 (5.1)   
Yes  4 (66.7)  30.5 (3.6–377.1)  .001 
Procalcitonin >100ng/mL
No  27  1 (3.7)   
Yes  2 (40.0)  14.7 (0.9–526.1)  .068 
Disseminated intravascular coagulation
No  39  3 (7.7)   
Yes  3 (50.0)  10.9 (1.4–94.7)  .025 
Base excess <–8
No  16  1 (6.2)   
Yes  1 (25.0)  4.5 (0.1–206.4)  .400 
Platelet * Neutrophil product <40×109/L
No  44  5 (11.4)   
Yes  1 (100.0)  Not available  .133 
Leucocytesin cerebrospinal fluid <10/mm3
No  38  4 (10.5)   
Yes  0 (0.0)  0 (0.0–34.3)  .808 
a

p for a two-tailed Fisher's exact test.

Discussion

We found a decreasing incidence of IMD in Navarra between 2008 and 2014, as has been documented for the rest of Spain.4 The increased incidence in winter3 and the greater burden of disease in young children are consistent with the literature.1,2 As is the case in other Western countries, we found a significant predominance of serogroup B.19 The low incidence of cases caused by serogroup B is associated with the high vaccination coverage with the MenC vaccine in Spain.20

The most frequent clinical presentation was sepsis, but in the literature there is variation in the most predominant form—sepsis or meningitis—from study to study.11,21 Patients presenting with sepsis and sepsis–meningitis sought care before patients with other forms of disease, probably on account of the rapid progression and severity of these cases. Fever and exanthem, which are symptoms frequently described in cases of IMD,15,21,22 were the manifestations found most frequently at the time of diagnosis. The exanthem was not haemorrhagic in two out of ten patients, which is a relevant finding,7 as less serious infections in children often present with non-haemorrhagic exanthem. Consistent with other studies,10 a considerable proportion of patients presented with some sign of shock on arrival to the hospital. This fact is worth noting, as some of these signs manifest in the early stages7 and knowing how to recognise them is important for the purpose of early diagnosis.11,12 Meningeal signs were negative in almost one out of every two patients presenting with sepsis–meningitis or meningitis, possibly because they manifest at a later time or because they often do not develop in infants.7,11

The abnormal laboratory findings were consistent with the previous literature.15,23 The proportion of patients with elevated PCT was higher than the proportion with elevated C-reactive protein. This may be related to the rapid progression of most cases and supports the hypothesis that due to its earlier elevation,24 PCT is more useful in the diagnosis of meningococcal disease.25

In IMD, there is a massive activation of the inflammatory cascade and the coagulation pathway, which causes damage to the internal organs of the patients.2 The severity of this disease is evinced by the percentage of patients admitted to the PICU and the need for life support measures. Our findings are consistent with those of other authors as to lethality, mortality and mean length of stay,6 with most deaths occurring in the first 24h,11,21 and the frequency and type of sequelae.8,9

Many studies have analysed clinical and laboratory markers, alone or in the form of scales, as potential prognostic factors in IMD.16,26–32 In our study, sepsis without meningitis, seizure, and a score of less than 15 in the Glasgow Coma Scale were the clinical factors with the highest predictive value for a poor outcome. We did not find an association between the duration of symptoms and poor outcome, probably because the most severe cases tend to seek care earlier and counteract a worse initial prognosis with earlier initiation of care. The association with the presence of extensive or advanced exanthem was not statistically significant, but is nevertheless considered relevant in prognostication.7,30,33 Thrombocytopaenia and DIC were the laboratory parameters that best predicted a poor outcome. This is a relevant finding, as the platelet count is an accessible and economic test with a demonstrated predictive value27 that is used in various composite scales, such as the PN product.29

Protocols for the management of paediatric patients with IMD can incorporate thrombocytopaenia as a marker for poor prognosis, one that could be particularly useful in facilities in which more sophisticated tests for other markers are not available. Children with thrombocytopaenia or other abnormal laboratory findings compatible with DIC, as well as children presenting with sepsis but not meningitis, a score of less than 15 in the Glasgow Coma Scale or that experience seizures should be considered at high risk.

The findings of this study must be interpreted taking its limitations into account. Although our study included all cases of IMD in Navarra, the sample size was small and restricted to a specific geographical area. The retrospective design may have led to biases. We did not consider whether patients with IMD had previously visited their primary care clinic or collect data for other symptoms such as headache, vomiting or photophobia.15,21 We were unable to obtain the laboratory values for all the patients. In some cases that resulted in permanent sequelae or death, the PCT, BE and leukocytecountin CSF were not available, so the association of these parameters with a poor outcome may be stronger than found in our analysis. Furthermore, in most cases, BE was measured in samples of venous blood, and the presence of DIC, which was documented at more advanced stages, may have been given more weight than other factors. We did not analyse psychological sequelae.

The recent introduction in the market of the meningococcal B vaccine in Spain marks the dawn of a new era in the prevention of IMD. This new development will probably lead to changes in this disease in the near future, so the situation that we have described may serve as the starting point for new studies evaluating the impact of the new vaccine in coming years.

To conclude, despite the significant advances made in the prevention of IMD with the routine immunisation of children against serogroup C meningococcus, the disease continues to be a significant health problem in the paediatric age group. The early recognition of symptoms, the optimisation of initial treatment in emergency care settings and the urgent transfer of patients to facilities with a PICU are key strategies to reducing mortality and the incidence of sequelae in children with IMD.

Conflict of interests

The authors have no conflict of interests to declare.

Acknowledgments

We thank Dr Federico Martinón-Torres (and his colleagues), co-coordinator of the ESIGEM study, for his willingness to collaborate with us on this study.

References
[1]
L.H. Harrison, C.L. Trotter, M.E. Ramsay.
Global epidemiology of meningococcal disease.
[2]
N.E. Rosenstein, B.A. Perkins, D.S. Stephens, T. Popovic, J.M. Hughes.
Meningococcal disease.
N Engl J Med, 344 (2001), pp. 1378-1388
[3]
D.S. Stephens, B. Greenwood, P. Brandtzaeg.
Epidemic meningitis, meningococcaemia, and Neisseria meningitidis.
Lancet, 369 (2007), pp. 2196-2210
[4]
J.A. Soult Rubio, M. Munoz Saez.
[Invasive meningococcal disease].
An Pediatr (Barc), 62 (2005), pp. 297-303
[5]
Red Nacional de Vigilancia Epidemiológica. Enfermedad meningocócica en España. Análisis de la temporada 2012–2013. Available from http://www.isciii.es/ISCIII/es/contenidos/fd-servicios-cientifico-tecnicos/fd-vigilancias-alertas/fd-enfermedades/MNG_informe_2012-2013_confirmados.pdf [accessed 26.07.15]
[6]
R. Gil-Prieto, L. Garcia-Garcia, A. Alvaro-Meca, A. Gonzalez-Escalada, P. Viguera Ester, A. Gil de Miguel.
The burden of hospitalizations for meningococcal infection in Spain (1997–2008).
Vaccine, 29 (2011), pp. 5765-5770
[7]
Grupo de trabajo de la Guía de Práctica Clínica sobre el Manejo de la Enfermedad Meningocócica Invasiva. Guía de práctica clínica sobre el manejo de la enfermedad meningocócica invasiva. Ministerio de Sanidad, Servicios Sociales e Igualdad. Instituto Aragonés de Ciencias de la Salud; 2013. Available from: http://www.guiasalud.es/GPC/GPC_525_EMI_ICS_compl.pdf [accessed 12.10.15]
[8]
R.M. Viner, R. Booy, H. Johnson, W.J. Edmunds, L. Hudson, H. Bedford, et al.
Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study.
Lancet Neurol, 11 (2012), pp. 774-783
[9]
M. Sadarangani, D.W. Scheifele, S.A. Halperin, W. Vaudry, N. le Saux, R. Tsang, et al.
Outcomes of invasive meningococcal disease in adults and children in Canada between 2002 and 2011: a prospective cohort study.
Clin Infect Dis, 60 (2015), pp. e27-e35
[10]
H.R. Huang, H.L. Chen, S.M. Chu.
Clinical spectrum of meningococcal infection in infants younger than six months of age.
Chang Gung Med J, 29 (2006), pp. 107-113
[11]
M.J. Thompson, N. Ninis, R. Perera, R. Mayon-White, C. Phillips, L. Bailey, et al.
Clinical recognition of meningococcal disease in children and adolescents.
[12]
T.A. Haj-Hassan, M.J. Thompson, R.T. Mayn-White, N. Ninis, A. Harnden, L.F. Smith, et al.
Which early “red flag” symptoms identify children with meningococcal disease in primary care.
Br J Gen Pract, 61 (2011), pp. e97-e104
[13]
National Institute for Health and Clinical Excellence. Bacterial meningitis and meningococcal septicaemia. Management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care. NICE clinical guideline 1023 National Collaborating Centre for Women's and Children's Health; 2010. Available from: http://www.nice.org.uk/nicemedia/live/13027/49339/49339.pdf [accessed 08.10.15]
[14]
Alonso Salas MT, De Carlos Vicente JC, Gil Antón J, Pinto Fuentes I, Quintilla Martinez JM, Sánchez Díaz JI. Documento de consenso SECIP-SEUP sobre manejo de sepsis grave y shock séptico en pediatría. Available from: http://www.seup.org/pdf_public/pub/consenso_sepsis_shock.pdf [accessed 10.10.15]
[15]
S. Nadel, J.S. Kroll.
Diagnosis and management of meningococcal disease: the need for centralized care.
FEMS Microbiol Rev, 31 (2007), pp. 71-83
[16]
M. Montero-Martin, D.P. Inwald, E.D. Carrol, F. Martinon-Torres.
Prognostic markers of meningococcal disease in children: recent advances and future challenges.
Exp Rev Anti Infect Ther, 12 (2014), pp. 1357-1369
[17]
B. Goldstein, B. Giroir, A. Randolph.
International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.
Pediatr Crit Care Med, 6 (2005), pp. 2-8
[18]
R.L. Bick.
Disseminated intravascular coagulation current concepts of etiology, pathophysiology, diagnosis, and treatment.
Hematol Oncol Clin North Am, 17 (2003), pp. 149-176
[19]
J.R. MacNeil, N. Bennett, M.M. Farley, L.H. Harrison, R. Lynfield, M. Nichols, et al.
Epidemiology of infant meningococcal disease in the United States, 2006–2012.
Pediatrics, 135 (2015), pp. e305-e311
[20]
M. Garrido-Estepa, I. Leon-Gomez, R. Herruzo, R. Cano.
Changes in meningococcal C epidemiology and vaccine effectiveness after vaccine introduction and schedule modification.
Vaccine, 32 (2014), pp. 2604-2609
[21]
C. Sabatini, S. Bosis, M. Semino, L. Senatore, N. Principi, S. Esposito.
Clinical presentation of meningococcal disease in childhood.
J Prev Med Hyg, 53 (2012), pp. 116-119
[22]
M. Karanika, V.A. Vasilopoulou, A.T. Katsioulis, P. Papastergiou, M.N. Theodoridou, C.S. Hadjichristodoulou.
Diagnostic clinical and laboratory findings in response to predetermining bacterial pathogen: data from the Meningitis Registry.
[23]
G.D. Mills, H.M. Lala, M.R. Oehley, A.B. Craig, K. Barratt, D. Hood, et al.
Elevated procalcitonin as a diagnostic marker in meningococcal disease.
Eur J Clin Microbiol Infect Dis, 25 (2006), pp. 501-509
[24]
O. Maruk, K. Bestwick, A.P. Thomson, J.A. Sills, C.A. Hart.
Variation in serum C-reactive protein across the clinical spectrum of meningococcal disease.
Acta Paediatr, 82 (1993), pp. 729-733
[25]
E.D. Carrol, P. Newland, F.A. Riordan, A.P. Thomson, N. Curtis, C.A. Hart.
Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash.
Arch Dis Child, 86 (2002), pp. 282-285
[26]
E.D. Carrol, A.P. Thomson, A.P. Jones, G. Jeffers, C.A. Hart.
A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis.
Intensive Care Med, 31 (2005), pp. 1415-1419
[27]
R. Malley, W.C. Huskins, N. Kuppermann.
Multivariable predictive models for adverse outcome of invasive meningococcal disease in children.
J Pediatr, 129 (1996), pp. 702-710
[28]
D.C. Van der Kaay, E.D. de Kleijn, Y.B. de Rijke, W.C. Hop, R. de Groot, J.A. Hazelzet.
Procalcitonin as a prognostic marker in meningococcal disease.
Intensive Care Med, 28 (2002), pp. 1606-1612
[29]
M.J. Peters, R.I. Ross-Russell, D. White, S.J. Kerr, F.E. Eaton, I.N. Keengwe, et al.
Early severe neutropenia and thrombocytopenia identifies the highest risk cases of severe meningococcal disease.
Pediatr Crit Care Med, 2 (2001), pp. 225-231
[30]
J.F. Sinclair, C.H. Skeoch, D. Hallworth.
Prognosis of meningococcal septicaemia.
[31]
A. Castellanos-Ortega, M. Delgado-Rodriguez, J. Llorca, P. Sanchez Buron, S. Mencia Bartolome, A. Soult Rubio, et al.
A new prognostic scoring system for meningococcal septic shock in children. Comparison with three other scoring systems.
Intensive Care Med, 28 (2002), pp. 341-351
[32]
A. Blanco Quiros, J. Casado Flores, M. Nieto Moro, J.A. Garrote Adrados, E. Arranz Sanz, J. Asensio Anton.
Meningococcal sepsis in pediatrics. Parameters associated with poor outcome.
An Pediatr (Barc), 61 (2004), pp. 305-313
[33]
A.P. Thomson, J.A. Sills, C.A. Hart.
Validation of the Glasgow meningococcal septicemia prognostic score: a 10-year retrospective survey.
Critical Care Med, 19 (1991), pp. 26-30

Please cite this article as: Morales D, Moreno L, Herranz M, Bernaola E, Martínez-Baz I, Castilla J. Enfermedad meningocócica invasiva en Navarra en la era de la vacuna conjugada antimeningocócica C. An Pediatr (Barc). 2017;86:213–219.

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