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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The approach to a febrile infant aged less than 3 months continues to be a challenge&#46; The key issue is how to recognise when we are facing a potentially severe infection&#46; In recent years&#44; there have been changes in both the aetiology of severe infections and in the tools that are or are going to be at our disposal to approach their aetiological diagnosis&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">When it comes to infections of a bacterial aetiology in young infants&#44; two facts have changed the situation in Spain in recent years&#46; The first one is the policy for the prevention of early-onset neonatal sepsis adopted by obstetricians&#44; which has led to a clear decrease in the incidence of infection by <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#46; However&#44; it is unclear whether the incidence of late-onset sepsis has decreased in equal measure&#44; so we must remain to be aware of these infections past the first week of life&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> On the other hand&#44; the nearly universal vaccination against pneumococcus in Spain has produced a marked decrease in invasive disease due to <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> in every age group&#46; A study by de la Torre et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> confirmed these changing trends in the aetiology of bacterial infections in young infants&#44; and emphasised the importance of <span class="elsevierStyleItalic">Escherichia coli</span> as the leading causative agent of severe bacterial infections in this age group&#44; and therefore in the differential diagnosis of urinary tract infections&#44; its most frequent form of disease&#44; consistent with what has been described in other countries&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">But bacterial infections aside&#44; viruses&#44; which many do not associate with our patients&#44; are emerging as the causative agents of severe illness in this age group&#46; On one hand&#44; and mostly based on the North American literature&#44; there is infection by herpes simplex viruses&#44; which given its severity and the availability of an effective treatment&#8212;acyclovir&#8212;should be taken into consideration&#44; especially in the first month of life&#46; While the incidence in the United States is of 33 cases per 100<span class="elsevierStyleHsp" style=""></span>000 live births&#44; in some countries neighbouring Spain&#44; such as the United Kingdom&#44; the incidence is of 1&#46;65 cases per 100<span class="elsevierStyleHsp" style=""></span>000 births&#46; We do not have data on the incidence of neonatal herpes infections in Spain&#46; This means that we have no clear policy on whether or not to empirically treat herpes infections in the youngest infants with manifestations of sepsis&#44; and underscores the need to conduct studies on the subject&#46; De la Torre<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> reported the detection of only 3 cases of herpes infection out of 3400 assessed infants &#40;0&#46;08&#37;&#41;&#44; although the study had not been designed to determine the incidence of herpes infections and thus the results must be interpreted with caution&#46; The other groups of viruses that are involved in severe illness in this age group are enterovirus and parechovirus&#44; and the latter in particular&#46; Human parechovirus&#44; especially type 3&#44; has been recently recognised as a relatively frequent causative agent of fever without source and sepsis in young infants&#44; usually aged less than 2 months&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> often requiring admission to intensive care units&#46; Although the short-term outcome of these infections is good &#40;usually within a few hours&#41;&#44; these infants are treated as if they had a bacterial infection&#44; with administration of broad-spectrum antibiotics and often prolonged hospitalisations&#46; Both enterovirus and parechovirus can be detected in cerebrospinal fluid &#40;CSF&#41;&#44; but it is also possible to detect them in blood&#44; faeces or throat swab samples using polymerase chain reaction &#40;PCR&#41;&#46; One characteristic feature of parechovirus infection is the absence of pleocytosis even when the virus has been detected in CSF&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">All of the above requires that we reconsider our approach to the aetiological diagnosis of infants with fever without source&#46; Whether a lumbar puncture is necessary or not&#44; and in which patients&#44; is currently being debated&#46; The importance of ruling out a urinary tract infection seems unquestionable&#44; as this is the most common site of bacterial infection in Spain&#46; Also&#44; molecular virological tests for the rapid diagnosis of infection by herpes simplex virus&#44; enterovirus and parechovirus are clearly an invaluable tool in the evaluation of fever without source and suspected sepsis in this age group&#46; Once their routine use is widespread in microbiology laboratories of Spanish hospitals&#44; we will not only be able to make accurate diagnoses&#44; but also to avoid unnecessary treatments and protracted hospitalisations&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">I cannot conclude this reflection without a discussion of a seemingly near future in the search for techniques that will allow us to know whether we are facing a viral or a bacterial infection&#46; At present&#44; none of the currently used biological markers&#44; like C-reactive protein&#44; procalcitonin or other that are not as widespread&#44; have been shown to be able to discriminate bacterial infections with sufficient sensitivity and specificity&#46; The multiple scores combining clinical and laboratory data that have been developed have also failed to achieve this&#44; although they are useful for the management of patients&#46; To further complicate matters&#44; the coexistence of bacterial and viral infections is being described with increasing frequency&#46; There have been enormous advances in virological diagnostic techniques&#44; and today we are able to quickly and easily detect infections by various viruses at the bedside or within a few hours&#44; although this does not allow us to rule out the presence of bacterial infection with certainty&#44; especially in cases in which classical markers such as C-reactive protein are outside their normal range&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Research in recent years has focused on the fields of genomics and metabolomics&#44; and nanotechnology-based approaches for detecting host responses to infection and discriminating between viral and bacterial infections are being explored&#46; Various molecules and cytokines&#44; and even the possibility of developing simultaneous assay panels for several markers&#44; are currently being investigated&#46; Using transcriptomic&#44; proteomic or metabolomic techniques&#44; researchers are analysing the various responses of individuals to infection&#46; Gene expression profiling using microarray technology can simultaneously measure the messenger RNA of thousands of transcriptions&#46; This offers a rapid method for screening thousands of molecular species with a single assay&#46; Our goal would be to identify gene expression profiles in specific infections relative to others in order to determine whether the underlying infection is of viral&#44; bacterial or mixed aetiology&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Studies of this kind are being conducted in children of different ages&#46; We ought to comment on the study conducted by Mahajan et al&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> who used this technology to identify bacterial infections in febrile infants aged less than 60 days&#46; They identified 66 genes whose expression allowed the detection of bacterial infection with a sensitivity of 87&#37; and a specificity of 89&#37;&#46; In children with bacteraemia&#44; a 10-gene transcriptional profile had a sensitivity of 94&#37; and a specificity of 95&#37;&#44; improving on the yield of the Yale Observation Scale&#46; They also demonstrated that this technology could be used successfully in hospital emergency departments with samples of as little as 1<span class="elsevierStyleHsp" style=""></span>mL of blood&#46; Although these studies have limitations and their findings have yet to be confirmed&#44; the ground that is left to cover is steadily decreasing&#44; and in the not-so-distant future we may be able to determine whether our patients have&#8212;or not&#8212;a bacterial infection&#46;</p></span>"
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Editorial
Fever without source in infants less than 3 months of age. What's new?
Fiebre sin foco en lactantes menores de 3 meses. ¿Qué hay de nuevo?
Cristina Calvoa,
Corresponding author
, María de Ceano-Vivasb
a Servicio de Pediatría Hospitalaria, Enfermedades Infecciosas y Tropicales, Hospital Infantil La Paz (IdiPaz), Red de Investigación Traslacional en Infectología Pediátrica (RITIP), Madrid, Spain
b Servicio de Urgencias Pediátricas, Hospital Infantil La Paz, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The approach to a febrile infant aged less than 3 months continues to be a challenge&#46; The key issue is how to recognise when we are facing a potentially severe infection&#46; In recent years&#44; there have been changes in both the aetiology of severe infections and in the tools that are or are going to be at our disposal to approach their aetiological diagnosis&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">When it comes to infections of a bacterial aetiology in young infants&#44; two facts have changed the situation in Spain in recent years&#46; The first one is the policy for the prevention of early-onset neonatal sepsis adopted by obstetricians&#44; which has led to a clear decrease in the incidence of infection by <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#46; However&#44; it is unclear whether the incidence of late-onset sepsis has decreased in equal measure&#44; so we must remain to be aware of these infections past the first week of life&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> On the other hand&#44; the nearly universal vaccination against pneumococcus in Spain has produced a marked decrease in invasive disease due to <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> in every age group&#46; A study by de la Torre et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> confirmed these changing trends in the aetiology of bacterial infections in young infants&#44; and emphasised the importance of <span class="elsevierStyleItalic">Escherichia coli</span> as the leading causative agent of severe bacterial infections in this age group&#44; and therefore in the differential diagnosis of urinary tract infections&#44; its most frequent form of disease&#44; consistent with what has been described in other countries&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">But bacterial infections aside&#44; viruses&#44; which many do not associate with our patients&#44; are emerging as the causative agents of severe illness in this age group&#46; On one hand&#44; and mostly based on the North American literature&#44; there is infection by herpes simplex viruses&#44; which given its severity and the availability of an effective treatment&#8212;acyclovir&#8212;should be taken into consideration&#44; especially in the first month of life&#46; While the incidence in the United States is of 33 cases per 100<span class="elsevierStyleHsp" style=""></span>000 live births&#44; in some countries neighbouring Spain&#44; such as the United Kingdom&#44; the incidence is of 1&#46;65 cases per 100<span class="elsevierStyleHsp" style=""></span>000 births&#46; We do not have data on the incidence of neonatal herpes infections in Spain&#46; This means that we have no clear policy on whether or not to empirically treat herpes infections in the youngest infants with manifestations of sepsis&#44; and underscores the need to conduct studies on the subject&#46; De la Torre<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> reported the detection of only 3 cases of herpes infection out of 3400 assessed infants &#40;0&#46;08&#37;&#41;&#44; although the study had not been designed to determine the incidence of herpes infections and thus the results must be interpreted with caution&#46; The other groups of viruses that are involved in severe illness in this age group are enterovirus and parechovirus&#44; and the latter in particular&#46; Human parechovirus&#44; especially type 3&#44; has been recently recognised as a relatively frequent causative agent of fever without source and sepsis in young infants&#44; usually aged less than 2 months&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> often requiring admission to intensive care units&#46; Although the short-term outcome of these infections is good &#40;usually within a few hours&#41;&#44; these infants are treated as if they had a bacterial infection&#44; with administration of broad-spectrum antibiotics and often prolonged hospitalisations&#46; Both enterovirus and parechovirus can be detected in cerebrospinal fluid &#40;CSF&#41;&#44; but it is also possible to detect them in blood&#44; faeces or throat swab samples using polymerase chain reaction &#40;PCR&#41;&#46; One characteristic feature of parechovirus infection is the absence of pleocytosis even when the virus has been detected in CSF&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">All of the above requires that we reconsider our approach to the aetiological diagnosis of infants with fever without source&#46; Whether a lumbar puncture is necessary or not&#44; and in which patients&#44; is currently being debated&#46; The importance of ruling out a urinary tract infection seems unquestionable&#44; as this is the most common site of bacterial infection in Spain&#46; Also&#44; molecular virological tests for the rapid diagnosis of infection by herpes simplex virus&#44; enterovirus and parechovirus are clearly an invaluable tool in the evaluation of fever without source and suspected sepsis in this age group&#46; Once their routine use is widespread in microbiology laboratories of Spanish hospitals&#44; we will not only be able to make accurate diagnoses&#44; but also to avoid unnecessary treatments and protracted hospitalisations&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">I cannot conclude this reflection without a discussion of a seemingly near future in the search for techniques that will allow us to know whether we are facing a viral or a bacterial infection&#46; At present&#44; none of the currently used biological markers&#44; like C-reactive protein&#44; procalcitonin or other that are not as widespread&#44; have been shown to be able to discriminate bacterial infections with sufficient sensitivity and specificity&#46; The multiple scores combining clinical and laboratory data that have been developed have also failed to achieve this&#44; although they are useful for the management of patients&#46; To further complicate matters&#44; the coexistence of bacterial and viral infections is being described with increasing frequency&#46; There have been enormous advances in virological diagnostic techniques&#44; and today we are able to quickly and easily detect infections by various viruses at the bedside or within a few hours&#44; although this does not allow us to rule out the presence of bacterial infection with certainty&#44; especially in cases in which classical markers such as C-reactive protein are outside their normal range&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Research in recent years has focused on the fields of genomics and metabolomics&#44; and nanotechnology-based approaches for detecting host responses to infection and discriminating between viral and bacterial infections are being explored&#46; Various molecules and cytokines&#44; and even the possibility of developing simultaneous assay panels for several markers&#44; are currently being investigated&#46; Using transcriptomic&#44; proteomic or metabolomic techniques&#44; researchers are analysing the various responses of individuals to infection&#46; Gene expression profiling using microarray technology can simultaneously measure the messenger RNA of thousands of transcriptions&#46; This offers a rapid method for screening thousands of molecular species with a single assay&#46; Our goal would be to identify gene expression profiles in specific infections relative to others in order to determine whether the underlying infection is of viral&#44; bacterial or mixed aetiology&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Studies of this kind are being conducted in children of different ages&#46; We ought to comment on the study conducted by Mahajan et al&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> who used this technology to identify bacterial infections in febrile infants aged less than 60 days&#46; They identified 66 genes whose expression allowed the detection of bacterial infection with a sensitivity of 87&#37; and a specificity of 89&#37;&#46; In children with bacteraemia&#44; a 10-gene transcriptional profile had a sensitivity of 94&#37; and a specificity of 95&#37;&#44; improving on the yield of the Yale Observation Scale&#46; They also demonstrated that this technology could be used successfully in hospital emergency departments with samples of as little as 1<span class="elsevierStyleHsp" style=""></span>mL of blood&#46; Although these studies have limitations and their findings have yet to be confirmed&#44; the ground that is left to cover is steadily decreasing&#44; and in the not-so-distant future we may be able to determine whether our patients have&#8212;or not&#8212;a bacterial infection&#46;</p></span>"
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Article information
ISSN: 23412879
Original language: English
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Idiomas
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