Scientific Letter
Paediatric Multidrug Resistant Tuberculosis Outbreak in a Low Incidence Country: The Need for Better Diagnosic Tools and More Accessible Treatments
Read
1761
Timeswas read the article
570
Total PDF
1191
Total HTML
Share statistics
array:23 [ "pii" => "S0300289622006421" "issn" => "03002896" "doi" => "10.1016/j.arbres.2022.11.013" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3222" "copyright" => "SEPAR" "copyrightAnyo" => "2022" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2023;59:183-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0300289622005713" "issn" => "03002896" "doi" => "10.1016/j.arbres.2022.09.010" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3183" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Arch Bronconeumol. 2023;59:186-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Director</span>" "titulo" => "In Search for Simplicity: Quantifying the Diagnostic Algorithm of Hypersensitivity Pneumonitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "186" "paginaFinal" => "188" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4314 "Ancho" => 3341 "Tamanyo" => 1119598 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Application of the proposed punctuation to the diagnostic algorithm.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Luis Lopez-Campos, Cecilia Lopez-Ramírez, Angela Lopez-Bauza, Jose Antonio Rodriguez Portal" "autores" => array:4 [ 0 => array:2 [ "nombre" => "José Luis" "apellidos" => "Lopez-Campos" ] 1 => array:2 [ "nombre" => "Cecilia" "apellidos" => "Lopez-Ramírez" ] 2 => array:2 [ "nombre" => "Angela" "apellidos" => "Lopez-Bauza" ] 3 => array:2 [ "nombre" => "Jose Antonio" "apellidos" => "Rodriguez Portal" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622005713?idApp=UINPBA00003Z" "url" => "/03002896/0000005900000003/v4_202401230711/S0300289622005713/v4_202401230711/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0300289622005828" "issn" => "03002896" "doi" => "10.1016/j.arbres.2022.09.018" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "3194" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2023;59:180-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Variables Influencing Hospital Stay and 10-Year Staying Trending After Anatomical Lung Resection" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "180" "paginaFinal" => "182" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1221 "Ancho" => 1675 "Tamanyo" => 81573 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Graph showing changes in mean postoperative length of stay throughout the three time periods.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Teresa Gómez-Hernández, Clara Forcada, Marta Fuentes, Nuria Novoa, José Luis Aranda, Cristina Rivas, Gonzalo Varela, Marcelo F. Jiménez" "autores" => array:8 [ 0 => array:2 [ "nombre" => "María Teresa" "apellidos" => "Gómez-Hernández" ] 1 => array:2 [ "nombre" => "Clara" "apellidos" => "Forcada" ] 2 => array:2 [ "nombre" => "Marta" "apellidos" => "Fuentes" ] 3 => array:2 [ "nombre" => "Nuria" "apellidos" => "Novoa" ] 4 => array:2 [ "nombre" => "José Luis" "apellidos" => "Aranda" ] 5 => array:2 [ "nombre" => "Cristina" "apellidos" => "Rivas" ] 6 => array:2 [ "nombre" => "Gonzalo" "apellidos" => "Varela" ] 7 => array:2 [ "nombre" => "Marcelo F." "apellidos" => "Jiménez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622005828?idApp=UINPBA00003Z" "url" => "/03002896/0000005900000003/v4_202401230711/S0300289622005828/v4_202401230711/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Paediatric Multidrug Resistant Tuberculosis Outbreak in a Low Incidence Country: The Need for Better Diagnosic Tools and More Accessible Treatments" "tieneTextoCompleto" => true "saludo" => "To the Director," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "183" "paginaFinal" => "185" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Francesc Arasa Panisello, Berta Soler Febrer, Ana Maria Isabel Lima Cordón, Nelly Raquel García López, Elena Martínez García, Antoni Soriano-Arandes" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Francesc" "apellidos" => "Arasa Panisello" "email" => array:1 [ 0 => "arasafrancesc@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Berta" "apellidos" => "Soler Febrer" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Ana Maria Isabel" "apellidos" => "Lima Cordón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Nelly Raquel" "apellidos" => "García López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Elena" "apellidos" => "Martínez García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Antoni" "apellidos" => "Soriano-Arandes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Pediatrics Service. Hospital de Tortosa Verge de la Cinta, ICS, Tortosa, Catalonia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Paediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, ICS, Barcelona, Catalonia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Multidrug resistant tuberculosis (MDR-TB) is defined as TB disease caused by strains of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> with resistance to at least isoniazid and rifampicin.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In any childhood TB diagnosis procedure, major effort must be made to confirm the <span class="elsevierStyleItalic">M tuberculosis</span> strain and the drug susceptibility, as well as facilitating the access to the appropriate treatment.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The most common clinical form of TB in children is primary TB involving intrathoracic lymph nodes, with a very low bacillary load in their secretions. Despite recent advances, traditional bacteriological tests (bacilloscopy and culture) have a low diagnostic sensitivity (around 30%).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Therefore, even with negative test results, starting empirical treatment is recommended when faced with clinical and radiological suspicion.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Moreover, the treatment regimen in children is generally decided upon the results of the drug susceptibility test (DST) performed on the source case (mostly, an adult).<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> If the adult is diagnosed with a MDR-TB, the child will be treated as such, and even more so when we know that early initiation of appropriate treatment is essential to ensure good outcomes for both the individual and the community.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2013, the World Health Organization (WHO) endorsed <span class="elsevierStyleItalic">Xpert MTB/RIF® (Xpert; Cepheid, Sunnyvale, CA, USA)</span> for its use in children as an alternative to bacterial culture. It uses a closed, automated system for sample preparation, amplification and real-time polymerase chain reaction (PCR) detection of both <span class="elsevierStyleItalic">M. tuberculosis</span> and rifampicin resistance in only a few minutes.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleItalic">The Xpert MTB/RIF Ultra cartridge® (Cepheid, Sunnyvale, CA, USA)</span> was developed as the next-generation assay to overcome the suboptimal sensitivity in smear-negative TB patients when using the Xpert MTB/RIF<span class="elsevierStyleItalic">®</span> assay. The sensitivity of Xpert Ultra for detection of Mycobacterium tuberculosis was 64% (95% CI: 48–77%) in gastric aspirate samples and 53% (95% CI: 35–70%) in stool samples. The specificity was 95% in gastric aspirate samples (95% CI: 84–99%) and 98% in stool (CI: 93–99%). The benefit of detecting rifampicin resistance using Xpert Ultra was extrapolated from adult data.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> According to the recent 2021 WHO guidelines, it is strongly recommended as the initial diagnostic test for TB and rifampicin-resistance detection in sputum, gastric aspirate, and other samples rather than smear microscopy/culture and phenotypic drug sensitivity tests in all ages.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1,2,4,5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Our aim is to describe a MDR-TB outbreak in a family from a high-income country, Catalonia (Spain), in a low-incidence TB area, where the second-level reference hospital did not have direct access to perform the <span class="elsevierStyleItalic">Xpert</span> method for TB prompt diagnosis.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The primary case was a 5-year-old child with a diagnosis of a probable intrathoracic TB with pulmonary involvement. After twelve days of torpid pneumonia, the chest X-ray (CXR) was compatible with a primary TB with a Ghon complex affecting the right lower lobe and an enlargement of the hiliar lymph nodes. Tuberculin skin test (TST) was positive (13<span class="elsevierStyleHsp" style=""></span>mm), and smear exam was negative. TB treatment with four first-line drugs was started: isoniazid, rifampicin, pyrazinamide and ethambutol.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Through the contact tracing study, a smear positive adult (child's uncle) with bilateral pneumonia and a TST of 20<span class="elsevierStyleHsp" style=""></span>mm was detected, being considered as the source case. Culture for <span class="elsevierStyleItalic">M tuberculosis</span> was performed and he started the same TB regimen treatment as the child.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Other four adults and two children (aged 12 years and 18 months) were living in the same household, all of whom were asymptomatic. The adults were diagnosed with latent tuberculosis infection and treated with a combination of rifampicin and isoniazid. No TB preventive treatment (TPT) was initially prescribed for the 12-year-old girl, with a TST of 0<span class="elsevierStyleHsp" style=""></span>mm and a normal CXR. She was scheduled for a follow-up consultation two months later. The 18-month-old girl had a TST of 12<span class="elsevierStyleHsp" style=""></span>mm and a normal CXR, therefore she started TPT with isoniazid.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Two months later, culture for the primary case was reported as negative, and the antibiogram for the source case came back as resistant to isoniazid and rifampicin, and sensitive to fluoroquinolones and to injectable aminoglycosides.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding the contact cases, a TST conversion (0–25<span class="elsevierStyleHsp" style=""></span>mm) was observed in the asymptomatic 12-year-old girl, and a new CXR showed a consolidation in the left upper lobe with mediastinal widening, highly suggestive of TB. The 18-month-old child, asymptomatic, had mediastinal adenopathies in the thoracic CT scan. In both of them, bacilloscopy and <span class="elsevierStyleItalic">M tuberculosis</span> culture were negative.</p><p id="par0055" class="elsevierStylePara elsevierViewall">We notified a familial outbreak of MDR-TB affecting one adult and three children, neither of them immunosuppressed or HIV-infected. (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The MDR-TB treatment regimen has to include at least a daily administration of four-five oral second-line drugs<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5,6</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Although since 2022 the WHO recommends the use of bedaquiline in children of all ages with MDR-TB,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1,2</span></a> in Spain it is only conditionally authorized for patients over 12 years of age.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> Therefore it was not a treatment option in these patients.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Due to this, TB treatment for the 5-year-old boy was changed to a combination of levofloxacin (20<span class="elsevierStyleHsp" style=""></span>mg/kg/day), linezolid (12<span class="elsevierStyleHsp" style=""></span>mg/kg/day), delamanid (50<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h), cycloserine (20<span class="elsevierStyleHsp" style=""></span>mg/kg/dia) and clofazimine (5<span class="elsevierStyleHsp" style=""></span>mg/kg/48<span class="elsevierStyleHsp" style=""></span>h).</p><p id="par0075" class="elsevierStylePara elsevierViewall">For the source case, the adult infectologist indicated a change of treatment regime to a combination of moxifloxacin, linezolid, clofazimine and amikacin. The indication of the latter was due to the difficult access to delamanid and bedaquiline.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Both had received 2 months of useless standard first-line anti-TB treatment. Additionally, the two other asymptomatic children diagnosed with TB recieved the same MDR-TB treatment as the index case, also with a considerable delay (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0080" class="elsevierStylePara elsevierViewall">When talking about MDR-TB, some Sub Saharan African countries immediately come to mind, where the pooled prevalence for MDR-TB is 21%,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8,9</span></a> or some Eastern European countries stand out where a half of the TB cases are MDR-TB.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> In Spain most <span class="elsevierStyleItalic">M tuberculosis</span> strains are sensitive to first-line drugs, being 1.8% of TB cases resistant to rifampicin and 1.2% were MDR-TB in 2020.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Currently, the WHO recommends rapid molecular tests as the initial test to diagnose pulmonary TB and to simultaneously detect rifampicin resistance.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In 2020, in Spain, the percentage of notified TB patients diagnosed using WHO-recommended rapid tests (target<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>90%) was 31.9%, and first-line DST coverage among them (target<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>100%) was 46.8%, with a RR/MDR-TB case-detection rate (target<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>85%) of 10.4%.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">With this letter we want to highlight the ongoing difficulties for prompt TB diagnosis and for obtaining appropriate drugs for MDR-TB treatment in a high-income country with low TB incidence.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In the described outbreak, carrying out a molecular diagnosis test of the source case would have allowed initiation of appropriate treatment much earlier.</p><p id="par0105" class="elsevierStylePara elsevierViewall">In addition, we believe that the use of bedaquiline should not have age restrictions since it has been demonstrated to be safe in all ages.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">To conclude, we underline the need to harmonize our MDR-TB care protocols, with special reference to children and adolescents, following international guidelines; not only applying molecular tests for rapid TB diagnosis and sensitivity studies, but also in improving accessibility to second-line drugs with proven effectiveness and safety, such as bedaquiline.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0125" class="elsevierStylePara elsevierViewall">There was no funding sources in our research.</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">m: months, y: years, LTI: latent tuberculous infection, TB: tuberculosis.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient (sex and age) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First diagnosis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Standard treatment initiation \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MDR-TBDiagnostic confirmation or suspicion \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Delay in correct diagnosis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MDR-TB treatment initiation \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Delay in starting appropriate treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Boy, 5y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pneumonia and intrathoracic lymph nodes:TB suspicion15/FEB/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For TB17/FEB/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pneumonia and intrathoracic lymph nodes19/APR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">03/MAY/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Man, 27y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PneumoniaTB10/MAR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For TB10/MAR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pneumonia14/APR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">05/MAY/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Girl, 12y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exposition to TB04/MAR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Expectant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pneumonia and intrathoracic lymph nodes26/APR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">02/MAY/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Girl, 18m \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTI04/MAR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For LTI29/MAR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pneumonia and intrathoracic lymph nodes25/APR/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16/MAY/2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 days \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3441854.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients with TB disease in the referred outbreak. Delay in diagnosing and starting treatment correctly.</p>" ] ] 1 => array:9 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Adapted from Mirzayev F, Viney K, Linh NN, et al. World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update. Eur Respir J 2021; 57: 2003300. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1183/13993003.03300-2020">https://doi.org/10.1183/13993003.03300-2020</span>.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Steps \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicine \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Include all three drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Levofloxacin OR moxifloxacinBedaquilineLinezolid \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Add one or both drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ClofazimineCycloserine OR terizidone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Add to complete the regimen when drugs from groups A and B cannot be used \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DelamanidEthambutolPyrazinamideImipenem-cilastin ORMeropenemAmikacin OR StreptomycinEthionamide OR prothionamidep-Aminosalicylic acid \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3441855.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Grouping and steps to follow for second-line drugs indication, recommended for use in longer MDR-TB regimens.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO." ] ] ] 1 => array:3 [ "identificador" => "bib0065" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Rapid communication on updated guidance on the management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO." ] ] ] 2 => array:3 [ "identificador" => "bib0070" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic advances in childhood tuberculosis—improving specimen collection and yield of microbiological diagnosis for intrathoracic tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Wobudeya" 1 => "M. Bonnet" 2 => "E.G. Walters" 3 => "P. Nabeta" 4 => "R. Song" 5 => "W. Murithi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/pathogens11040389" "Revista" => array:5 [ "tituloSerie" => "Pathogens" "fecha" => "2022" "volumen" => "11" "paginaInicial" => "389" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35456064" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0075" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "WHO consolidated guidelines on tuberculosis. Module 3: diagnosis – rapid diagnostics for tuberculosis detection, 2021 update. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. <a target="_blank" href="https://www.who.int/publications/i/item/9789240029415">https://www.who.int/publications/i/item/9789240029415</a>." ] ] ] 4 => array:3 [ "identificador" => "bib0080" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Management of drug-resistant tuberculosis in children: a field guide. Boston, USA: The Sentinel Project for Pediatric Drug-Resistant Tuberculosis; November 2021, Fifth edition." ] ] ] 5 => array:3 [ "identificador" => "bib0085" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Mirzayev F, Viney K, Linh NN, et al. World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update. Eur Respir J 2021;57:2003300. <a target="_blank" href="https://doi.org/10.1183/13993003.03300-2020">https://doi.org/10.1183/13993003.03300-2020</a>." ] ] ] 6 => array:3 [ "identificador" => "bib0090" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Ministerio de Sanidad y Consumo. Agencia Española del Medicamento y Productos Sanitarios. Informe de Posicionamiento Terapéutico PT/V2/20102022 Informe de Posicionamiento Terapéutico de Bedaquilina (Sirturo®) Fecha de actualización. <a target="_blank" href="https://www.aemps.gob.es/">https://www.aemps.gob.es</a> [20.10.22]." ] ] ] 7 => array:3 [ "identificador" => "bib0095" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Tuberculosis-Africa CDC. <a target="_blank" href="https://africacdc.org/disease/tuberculosis/">https://africacdc.org/disease/tuberculosis/</a>." ] ] ] 8 => array:3 [ "identificador" => "bib0100" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of multidrug-resistant tuberculosis in East Africa: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.A. Molla" 1 => "M.A. Reta" 2 => "Y.Y. Ayene" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0270272" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2022" "volumen" => "17" "paginaInicial" => "e0270272" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35771884" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0105" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "European Center for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022-2020 data. Stockholm: ECDC; 2022. <a target="_blank" href="https://www.ecdc.europa.eu/en/publications-data/tuberculosis-surveillance-and-monitoring-europe-2022-2020-data">https://www.ecdc.europa.eu/en/publications-data/tuberculosis-surveillance-and-monitoring-europe-2022-2020-data</a>." ] ] ] 10 => array:3 [ "identificador" => "bib0110" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness and safety of delamanid- or bedaquiline-containing regimens among children and adolescents with multidrug resistant or extensively drug resistant tuberculosis: A nationwide study from Belarus, 2015–19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Solodovnikova" 1 => "A.M.V. Kumar" 2 => "H. Hurevich" 3 => "Y. Sereda" 4 => "V. Auchynka" 5 => "D. Katovich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4081/monaldi.2021.1646" "Revista" => array:3 [ "tituloSerie" => "Monaldi Arch Chest Dis" "fecha" => "2021" "volumen" => "91" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000005900000003/v4_202401230711/S0300289622006421/v4_202401230711/en/main.assets" "Apartado" => array:4 [ "identificador" => "93866" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005900000003/v4_202401230711/S0300289622006421/v4_202401230711/en/main.pdf?idApp=UINPBA00003Z&text.app=https://www.archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622006421?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 29 | 17 | 46 |
| 2024 September | 47 | 15 | 62 |
| 2024 August | 65 | 31 | 96 |
| 2024 July | 46 | 22 | 68 |
| 2024 June | 61 | 23 | 84 |
| 2024 May | 69 | 25 | 94 |
| 2024 April | 38 | 27 | 65 |
| 2024 March | 44 | 18 | 62 |
| 2024 February | 30 | 23 | 53 |
| 2024 January | 37 | 28 | 65 |
| 2023 December | 28 | 21 | 49 |
| 2023 November | 58 | 34 | 92 |
| 2023 October | 70 | 38 | 108 |
| 2023 September | 54 | 31 | 85 |
| 2023 August | 48 | 30 | 78 |
| 2023 July | 44 | 22 | 66 |
| 2023 June | 35 | 12 | 47 |
| 2023 May | 48 | 22 | 70 |
| 2023 April | 67 | 44 | 111 |
| 2023 March | 262 | 73 | 335 |
| 2023 February | 0 | 3 | 3 |
| 2023 January | 1 | 0 | 1 |
| 2022 December | 10 | 11 | 21 |
Show all
