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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">According to the World Health Organization &#40;WHO&#41;&#44; in 2014 there were 1 million of estimated cases of tuberculosis &#40;TB&#41; among children&#44; representing the 10&#37; of the global TB burden&#44; and 136&#44;000 children died because of TB&#46; However&#44; only 6&#46;5&#37; of the total 6 million of cases notified globally were children&#44; thus less than 400&#44;000 paediatric cases&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Childhood TB in fact is a hidden epidemics&#58; a large proportion of these cases remained undetected&#44; or not reported&#44; and what we see is only the top of the iceberg&#46; For many years&#44; TB control programs have been focused on adults with sputum microscopy smear-positive pulmonary disease&#44; which is the main responsible of TB spread&#44; and have not spent much attention to the unseen world of paediatric TB&#46; Additionally&#44; gaps in reporting paediatric TB cases from public and private health sectors&#44; and weak national age specific surveillance systems in many settings&#44; have contributed to maintain uncertainty about the paediatric TB burden&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The management of TB in children is challenging&#44; first because of the limited and delayed suspicion of TB&#44; due to the lack of specificity of signs and symptoms&#44; and the torpid clinical evolution in this population&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Furthermore&#44; performing an accurate diagnosis is difficult&#44; as the disease in children is generally pauci-bacillary&#44; the sputum is seldom produced&#44; especially by young children&#44; specimens are hard to obtain&#44; and diagnostic tools have limited sensitivity&#46; The diagnosis in most of cases is clinical&#44; and only rarely bacteriologically confirmed&#46; The history of contact with an adult with active disease is a useful information to support the diagnosis&#44; and well-characterized symptoms may help the diagnostic accuracy in older children&#44; while they may be less specific in very young children&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">However&#44; rapid molecular tests such as the geneXpert MTB&#47;RIF&#44; which has become widely available in the last few years&#44; have changed the diagnostic landscape of TB&#46; This performs the test&#44; thanks to its sensitivity&#44; much higher than microscopy&#44; in a short time requested &#40;only a couple of hours&#41;&#44; and there is no need of sophisticated laboratory infrastructure&#44; as compared to culture&#46; Molecular technology can contribute to improve TB diagnostic in the paediatric population&#44; and recent studies show that it increases two-folds the diagnosis of bacteriologically confirmed TB&#44; compared to microscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Additionally geneXpert shows a good sensitivity also on extra-pulmonary samples &#8211; especially in lymph nodes aspirates and in cerebrospinal fluid&#44; and can contribute to diagnose extra-pulmonary &#40;EP&#41; forms of TB&#46; WHO recommends its use in children suspects of TB meningitis and other forms of EP TB&#44; as lymph nodes TB&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Lastly&#44; geneXpert has the advantage of detecting also the resistance to rifampicin&#44; and therefore MDR-TB&#44; at the same time of the TB diagnosis&#44; and to exclude infections caused by Mycobacteria other than tuberculosis&#44; since that it only detects <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The challenge of getting an appropriate sample to test remains&#44; but there are interesting experiences showing various combinations of methods to improve specimen collections that&#44; together with the utilisation of PCR techniques&#44; can change significantly the chance of getting an accurate diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In addition to the challenges to diagnose TB disease&#44; children face various issues also to access appropriate treatment&#46; Not only because of the difficulty in swelling pills&#44; but also because of the challenges to achieve the right dosage and blood concentration&#44; to obtain efficacy of the therapy and to avoid toxicity&#46; Actually&#44; having a very low bacillary load&#44; children could be cured with even only three drugs&#46; In fact a fourth drug&#44; ethambutol&#44; is recommended only in the case of extensive lesions&#44; and in settings where there is high level of resistance to isoniazide or of HIV prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Even in the case of MDR-TB&#44; in the last WHO 2016 guidelines it has been accepted that children can be treated with a regimen that includes three new drugs&#44; without the need of the second line injectable &#40;WHO&#41; &#8211; except when there is bacteriological confirmation or large lungs involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The article of Perez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> addresses very well the challenges related to the access to appropriate TB treatment in children&#44; and it provides great insights on the characteristics of first line anti-TB drugs&#44; and on the implication of using them in soluble version versus solid pill&#44; and in fixed dose combination &#40;FDC&#41; versus single drugs&#46; Additionally&#44; the authors propose pragmatic and concrete recommendations to make an optimal use of the existing formulations available in Spain&#44; and advocate for early introduction of new FDCs&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In fact&#44; child-friendly first line TB formulations have become recently available in the market&#44; and through the Global Drug Facility&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Spain reports one of the highest number of childhood TB cases among the European Countries&#44; with the majority of them native born&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> but with an important increase of the proportion of cases diagnosed among immigrants in the last decades&#58; from 2&#37; to 46&#37; in a thirty years review&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Knowing the TB burden in the paediatric population&#44; globally and at country level&#44; is fundamental to encourage country regulatory authorities to facilitate the process of introduction of new drugs and preparations&#44; as well as to serve as an incentive for manufacturers to develop or market appropriate paediatric formulations&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> In fact&#44; appropriate drugs to treat optimally TB in children are essential&#44; especially in those very young or co-infected with HIV&#44; where there is a high risk of severe and rapidly disseminating forms of disease&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A large gap still exists in the case of multi-drug resistant and extensively resistant tuberculosis &#40;MDR&#47;XDR-TB&#41;&#44; where formulations adapted to children are not available yet&#46; This may be not much relevant in Spain&#44; where the percentage of primary MDR-TB in the native population seems very low &#40;0&#46;1&#37; vs&#46; 2&#46;2&#37; of immigrants&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> but it is very important in other countries of the European Region&#44; which seem to contribute importantly to the burden of paediatric drug-resistant TB&#44; based on mathematical modelling studies&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Again&#44; a better understanding of the treatments&#8217; needs would help to forecast markets and to create demand&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Encouragingly&#44; in the recent years there has been an increased interest on paediatric TB&#46; A roadmap of childhood TB has been launched&#44; new guidelines have been developed by the WHO&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> the number of scientific publications addressing children and TB is growing every year&#44; and additionally&#44; more clinical trials on new drugs include children at earlier stages than before&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> The paper of Perez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> contributes greatly to this global interest with pragmatic and concrete solutions&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Finally&#44; however&#44; it needs to be reminded that if we want to properly treat children with TB &#8211; and to generate demand for adequate drugs &#8211; first we need to find the paediatric cases&#46; Addressing the challenges of TB diagnosis in children through better access to more sensitive point of care diagnostic tools is needed&#44; together with better access to appropriate treatment&#46; The WHO End TB Strategy<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> sets ambitious targets&#44; including a substantial reduction of TB incidence and mortality&#44; and it provides opportunities to address paediatric TB at large scale&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#44; however the presented content of this article only expresses the personal opinion of the authors&#46;</p></span></span>"
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Editorial
Tuberculosis in children. Challenges and opportunities
Tuberculosis en niños. Retos y oportunidades
Jose A. Camineroa,b,
Corresponding author
jcamlun@gobiernodecanarias.org

Corresponding author.
, Anna Scardiglic
a Servicio de Neumología, Hospital General de Gran Canaria «Dr. Negrín», Las Palmas, Spain
b Unidad de Tuberculosis Multi-drogo-resistente, División de Tuberculosis, Unión Internacional Contra la Tuberculosis y Enfermedades Respiratorias, París, France
c Fondo Mundial para la Lucha contra el Sida, la Tuberculosis y la Malaria, Ginebra, Switzerland
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">According to the World Health Organization &#40;WHO&#41;&#44; in 2014 there were 1 million of estimated cases of tuberculosis &#40;TB&#41; among children&#44; representing the 10&#37; of the global TB burden&#44; and 136&#44;000 children died because of TB&#46; However&#44; only 6&#46;5&#37; of the total 6 million of cases notified globally were children&#44; thus less than 400&#44;000 paediatric cases&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Childhood TB in fact is a hidden epidemics&#58; a large proportion of these cases remained undetected&#44; or not reported&#44; and what we see is only the top of the iceberg&#46; For many years&#44; TB control programs have been focused on adults with sputum microscopy smear-positive pulmonary disease&#44; which is the main responsible of TB spread&#44; and have not spent much attention to the unseen world of paediatric TB&#46; Additionally&#44; gaps in reporting paediatric TB cases from public and private health sectors&#44; and weak national age specific surveillance systems in many settings&#44; have contributed to maintain uncertainty about the paediatric TB burden&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The management of TB in children is challenging&#44; first because of the limited and delayed suspicion of TB&#44; due to the lack of specificity of signs and symptoms&#44; and the torpid clinical evolution in this population&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Furthermore&#44; performing an accurate diagnosis is difficult&#44; as the disease in children is generally pauci-bacillary&#44; the sputum is seldom produced&#44; especially by young children&#44; specimens are hard to obtain&#44; and diagnostic tools have limited sensitivity&#46; The diagnosis in most of cases is clinical&#44; and only rarely bacteriologically confirmed&#46; The history of contact with an adult with active disease is a useful information to support the diagnosis&#44; and well-characterized symptoms may help the diagnostic accuracy in older children&#44; while they may be less specific in very young children&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">However&#44; rapid molecular tests such as the geneXpert MTB&#47;RIF&#44; which has become widely available in the last few years&#44; have changed the diagnostic landscape of TB&#46; This performs the test&#44; thanks to its sensitivity&#44; much higher than microscopy&#44; in a short time requested &#40;only a couple of hours&#41;&#44; and there is no need of sophisticated laboratory infrastructure&#44; as compared to culture&#46; Molecular technology can contribute to improve TB diagnostic in the paediatric population&#44; and recent studies show that it increases two-folds the diagnosis of bacteriologically confirmed TB&#44; compared to microscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Additionally geneXpert shows a good sensitivity also on extra-pulmonary samples &#8211; especially in lymph nodes aspirates and in cerebrospinal fluid&#44; and can contribute to diagnose extra-pulmonary &#40;EP&#41; forms of TB&#46; WHO recommends its use in children suspects of TB meningitis and other forms of EP TB&#44; as lymph nodes TB&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Lastly&#44; geneXpert has the advantage of detecting also the resistance to rifampicin&#44; and therefore MDR-TB&#44; at the same time of the TB diagnosis&#44; and to exclude infections caused by Mycobacteria other than tuberculosis&#44; since that it only detects <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The challenge of getting an appropriate sample to test remains&#44; but there are interesting experiences showing various combinations of methods to improve specimen collections that&#44; together with the utilisation of PCR techniques&#44; can change significantly the chance of getting an accurate diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In addition to the challenges to diagnose TB disease&#44; children face various issues also to access appropriate treatment&#46; Not only because of the difficulty in swelling pills&#44; but also because of the challenges to achieve the right dosage and blood concentration&#44; to obtain efficacy of the therapy and to avoid toxicity&#46; Actually&#44; having a very low bacillary load&#44; children could be cured with even only three drugs&#46; In fact a fourth drug&#44; ethambutol&#44; is recommended only in the case of extensive lesions&#44; and in settings where there is high level of resistance to isoniazide or of HIV prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Even in the case of MDR-TB&#44; in the last WHO 2016 guidelines it has been accepted that children can be treated with a regimen that includes three new drugs&#44; without the need of the second line injectable &#40;WHO&#41; &#8211; except when there is bacteriological confirmation or large lungs involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The article of Perez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> addresses very well the challenges related to the access to appropriate TB treatment in children&#44; and it provides great insights on the characteristics of first line anti-TB drugs&#44; and on the implication of using them in soluble version versus solid pill&#44; and in fixed dose combination &#40;FDC&#41; versus single drugs&#46; Additionally&#44; the authors propose pragmatic and concrete recommendations to make an optimal use of the existing formulations available in Spain&#44; and advocate for early introduction of new FDCs&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In fact&#44; child-friendly first line TB formulations have become recently available in the market&#44; and through the Global Drug Facility&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Spain reports one of the highest number of childhood TB cases among the European Countries&#44; with the majority of them native born&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> but with an important increase of the proportion of cases diagnosed among immigrants in the last decades&#58; from 2&#37; to 46&#37; in a thirty years review&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Knowing the TB burden in the paediatric population&#44; globally and at country level&#44; is fundamental to encourage country regulatory authorities to facilitate the process of introduction of new drugs and preparations&#44; as well as to serve as an incentive for manufacturers to develop or market appropriate paediatric formulations&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> In fact&#44; appropriate drugs to treat optimally TB in children are essential&#44; especially in those very young or co-infected with HIV&#44; where there is a high risk of severe and rapidly disseminating forms of disease&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A large gap still exists in the case of multi-drug resistant and extensively resistant tuberculosis &#40;MDR&#47;XDR-TB&#41;&#44; where formulations adapted to children are not available yet&#46; This may be not much relevant in Spain&#44; where the percentage of primary MDR-TB in the native population seems very low &#40;0&#46;1&#37; vs&#46; 2&#46;2&#37; of immigrants&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> but it is very important in other countries of the European Region&#44; which seem to contribute importantly to the burden of paediatric drug-resistant TB&#44; based on mathematical modelling studies&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Again&#44; a better understanding of the treatments&#8217; needs would help to forecast markets and to create demand&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Encouragingly&#44; in the recent years there has been an increased interest on paediatric TB&#46; A roadmap of childhood TB has been launched&#44; new guidelines have been developed by the WHO&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> the number of scientific publications addressing children and TB is growing every year&#44; and additionally&#44; more clinical trials on new drugs include children at earlier stages than before&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> The paper of Perez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> contributes greatly to this global interest with pragmatic and concrete solutions&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Finally&#44; however&#44; it needs to be reminded that if we want to properly treat children with TB &#8211; and to generate demand for adequate drugs &#8211; first we need to find the paediatric cases&#46; Addressing the challenges of TB diagnosis in children through better access to more sensitive point of care diagnostic tools is needed&#44; together with better access to appropriate treatment&#46; The WHO End TB Strategy<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> sets ambitious targets&#44; including a substantial reduction of TB incidence and mortality&#44; and it provides opportunities to address paediatric TB at large scale&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#44; however the presented content of this article only expresses the personal opinion of the authors&#46;</p></span></span>"
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Article information
ISSN: 23412879
Original language: English
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Idiomas
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?