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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In 1950 the World Health Organization &#40;WHO&#41; recognition of the public health threat caused by bovine tuberculosis led governments to implement control measures&#59; these included the pasteurization of milk&#44; rigorous inspection of carcasses in slaughterhouses&#44; the culling of cattle with positive tuberculin tests and prohibiting animals from leaving infected farms&#46; By these measures bovine tuberculosis was controlled or even eradicated&#46; The tuberculosis due to <span class="elsevierStyleItalic">Mycobacterium bovis</span> &#40;<span class="elsevierStyleItalic">M&#46; bovis</span>&#41; is now&#44; therefore&#44; an occupational zoonosis&#44; with the risk groups coming from rural communities&#44; farmers and handlers of cattle&#44; workers of the meat industry&#44; veterinarians and zoological garden workers&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Nowadays human infection by <span class="elsevierStyleItalic">M&#46; bovis</span> is considered rare in developed countries&#44; accounting for about 1&#37; of all human tuberculosis cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;7</span></a> The laboratory identification of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> complex &#40;MTC&#41; provides the clinical diagnosis of tuberculosis&#46; The species <span class="elsevierStyleItalic">M&#46; tuberculosis</span> and <span class="elsevierStyleItalic">M&#46; bovis</span>&#44; among others&#44; belong to this complex&#46; Although genotypically very similar&#44; <span class="elsevierStyleItalic">M&#46; bovis</span> is less easily transmitted between humans and is intrinsically resistant to pyrazinamide&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;8&#44;9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Based on this characteristic&#44; the Dire&#231;&#227;o Geral de Sa&#250;de &#40;General Directorate of Health&#44; DGS&#41; has recently published Guideline 13&#47;2010&#44; in which it recommends performing drug susceptibility testing &#40;DST&#41; on all first-line anti-tuberculosis drugs &#40;differentiating isoniazid&#44; rifampicin&#44; streptomycin&#44; ethambutol and pyrazinamide&#41; in all isolates of <span class="elsevierStyleItalic">M&#46; tuberculosis</span> complex and further subspecies differentiation when a pyrazinamide resistance isolate is found&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> It should be noted that the article 9&#47;DT from DGS about first-line DST&#44; in place since the year 2000&#44; does not list the drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This antibiotic&#44; in the context of laboratory diagnosis&#44; is not in the batch of anti-tuberculosis drugs to be first-line tested&#44; although it is commonly used in first-line therapeutic regimens&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Testing it requires a different laboratory methodology from other DST&#44; since this drug is only active in an acid environment&#46; In a number of laboratories this test is performed whenever resistance to at least one of the remaining first-line drugs occurs&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The latest international recommendations&#44; from the WHO and from the European Centre for Disease Prevention and Control &#40;ECDC&#41;&#44; do not include this drug in the group of the anti-tuberculosis drugs to be routinely tested&#46; Both organizations refer to the low reproducibility and consequently unreliable results&#46; WHO has emphasized also the expense&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The unit cost of these tests was calculated based on the selling prices to Administra&#231;&#227;o Regional de Sa&#250;de do Norte &#40;Northern Regional Health Administration&#41; of a reagents kit required for DST implementation through a liquid culture system &#40;BACTEC MGIT 960&#44; Becton and Dickinson&#44; Maryland&#44; USA&#41;&#46; The pyrazinamide susceptibility test costs around &#8364;45&#44; almost three times as much as the other first-line DST&#46; For a total cost evaluation of a test one would need to add the extra time spent&#44; as well as costs of other reagents and laboratory material such as&#58; suspension mediums&#44; ethyl alcohol&#44; bidistilled water&#44; micropipette tips&#44; syringes&#44; needles&#44; etc&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The DGS Guidance&#44; at a national level&#44; will lead to thousands of pyrazinamide susceptibility tests per year&#44; with an increased outflow of hundreds of thousands of Euros&#44; which poses the question whether this can be really justified&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The arguments against&#44; in addition to the international guidelines&#44; also include the fact that studies that have been carried out have shown that the screening of <span class="elsevierStyleItalic">M&#46; bovis</span>&#44; based on pyrazinamide monoresistance&#44; has a low positive predictive value&#44; as well as others that have revealed the existence of <span class="elsevierStyleItalic">M&#46; bovis</span> strains with other anti-tuberculosis resistance patterns&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Guideline 13&#47;2010 from DGS is based on the significant increase in bovine tuberculosis&#59; however&#44; it is also clear that&#44; nowadays&#44; the <span class="elsevierStyleItalic">M&#46; bovis</span> infection in human beings is&#44; in practice&#44; restricted to the risk groups&#46; It would be very good if we could count on new prevention strategies&#44; such as better communication between veterinary and human health working groups&#44; to identify patients who are most susceptible to the disease&#46; The pyrazinamide susceptibility test could then be performed on isolates from samples of these specific users and its cost&#47;benefit ratio improved&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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Pyrazinamide susceptibility testing in all isolates of the Mycobacterium tuberculosis complex – a critical analysis
Testes de sensibilidade à pirazinamida em todos os isolados do complexo Mycobacterium tuberculosis – uma análise crítica
J. Cunha
Laboratório de Micobacteriologia do Centro de Diagnóstico Pneumológico do Porto, Administração Regional de Saúde do Norte, Porto, Portugal
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    "titulo" => "Pyrazinamide susceptibility testing in all isolates of the <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> complex &#8211; a critical analysis"
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        "titulo" => "Testes de sensibilidade &#224; pirazinamida em todos os isolados do complexo <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> &#8211; uma an&#225;lise cr&#237;tica"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In 1950 the World Health Organization &#40;WHO&#41; recognition of the public health threat caused by bovine tuberculosis led governments to implement control measures&#59; these included the pasteurization of milk&#44; rigorous inspection of carcasses in slaughterhouses&#44; the culling of cattle with positive tuberculin tests and prohibiting animals from leaving infected farms&#46; By these measures bovine tuberculosis was controlled or even eradicated&#46; The tuberculosis due to <span class="elsevierStyleItalic">Mycobacterium bovis</span> &#40;<span class="elsevierStyleItalic">M&#46; bovis</span>&#41; is now&#44; therefore&#44; an occupational zoonosis&#44; with the risk groups coming from rural communities&#44; farmers and handlers of cattle&#44; workers of the meat industry&#44; veterinarians and zoological garden workers&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Nowadays human infection by <span class="elsevierStyleItalic">M&#46; bovis</span> is considered rare in developed countries&#44; accounting for about 1&#37; of all human tuberculosis cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;7</span></a> The laboratory identification of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> complex &#40;MTC&#41; provides the clinical diagnosis of tuberculosis&#46; The species <span class="elsevierStyleItalic">M&#46; tuberculosis</span> and <span class="elsevierStyleItalic">M&#46; bovis</span>&#44; among others&#44; belong to this complex&#46; Although genotypically very similar&#44; <span class="elsevierStyleItalic">M&#46; bovis</span> is less easily transmitted between humans and is intrinsically resistant to pyrazinamide&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;8&#44;9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Based on this characteristic&#44; the Dire&#231;&#227;o Geral de Sa&#250;de &#40;General Directorate of Health&#44; DGS&#41; has recently published Guideline 13&#47;2010&#44; in which it recommends performing drug susceptibility testing &#40;DST&#41; on all first-line anti-tuberculosis drugs &#40;differentiating isoniazid&#44; rifampicin&#44; streptomycin&#44; ethambutol and pyrazinamide&#41; in all isolates of <span class="elsevierStyleItalic">M&#46; tuberculosis</span> complex and further subspecies differentiation when a pyrazinamide resistance isolate is found&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> It should be noted that the article 9&#47;DT from DGS about first-line DST&#44; in place since the year 2000&#44; does not list the drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This antibiotic&#44; in the context of laboratory diagnosis&#44; is not in the batch of anti-tuberculosis drugs to be first-line tested&#44; although it is commonly used in first-line therapeutic regimens&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Testing it requires a different laboratory methodology from other DST&#44; since this drug is only active in an acid environment&#46; In a number of laboratories this test is performed whenever resistance to at least one of the remaining first-line drugs occurs&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The latest international recommendations&#44; from the WHO and from the European Centre for Disease Prevention and Control &#40;ECDC&#41;&#44; do not include this drug in the group of the anti-tuberculosis drugs to be routinely tested&#46; Both organizations refer to the low reproducibility and consequently unreliable results&#46; WHO has emphasized also the expense&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The unit cost of these tests was calculated based on the selling prices to Administra&#231;&#227;o Regional de Sa&#250;de do Norte &#40;Northern Regional Health Administration&#41; of a reagents kit required for DST implementation through a liquid culture system &#40;BACTEC MGIT 960&#44; Becton and Dickinson&#44; Maryland&#44; USA&#41;&#46; The pyrazinamide susceptibility test costs around &#8364;45&#44; almost three times as much as the other first-line DST&#46; For a total cost evaluation of a test one would need to add the extra time spent&#44; as well as costs of other reagents and laboratory material such as&#58; suspension mediums&#44; ethyl alcohol&#44; bidistilled water&#44; micropipette tips&#44; syringes&#44; needles&#44; etc&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The DGS Guidance&#44; at a national level&#44; will lead to thousands of pyrazinamide susceptibility tests per year&#44; with an increased outflow of hundreds of thousands of Euros&#44; which poses the question whether this can be really justified&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The arguments against&#44; in addition to the international guidelines&#44; also include the fact that studies that have been carried out have shown that the screening of <span class="elsevierStyleItalic">M&#46; bovis</span>&#44; based on pyrazinamide monoresistance&#44; has a low positive predictive value&#44; as well as others that have revealed the existence of <span class="elsevierStyleItalic">M&#46; bovis</span> strains with other anti-tuberculosis resistance patterns&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Guideline 13&#47;2010 from DGS is based on the significant increase in bovine tuberculosis&#59; however&#44; it is also clear that&#44; nowadays&#44; the <span class="elsevierStyleItalic">M&#46; bovis</span> infection in human beings is&#44; in practice&#44; restricted to the risk groups&#46; It would be very good if we could count on new prevention strategies&#44; such as better communication between veterinary and human health working groups&#44; to identify patients who are most susceptible to the disease&#46; The pyrazinamide susceptibility test could then be performed on isolates from samples of these specific users and its cost&#47;benefit ratio improved&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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ISSN: 21735115
Original language: English
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