Brief report
Tuberculosis in infants less than 3 months of age
Tuberculosis en lactantes menores de 3 meses
Teresa del Rosal Rabes
, Fernando Baquero-Artigao, Ana María Méndez-Echevarría, María José Mellado Peña
Corresponding author
Servicio de Pediatría Hospitalaria, Enfermedades Infecciosas y Tropicales Pediátricas, Hospital Universitario La Paz, Madrid, Spain
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The clinical manifestations and protocol are similar in both cases.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Its diagnosis is complicated as symptoms tend to be nonspecific and atypical. Furthermore, the tuberculin skin test (TST) often yields false negative results and the sensitivity of interferon-gamma release assays (IGRA) is lower than in older children.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> It is treated in the same way as infants over the age of 3 months, but there is very little pharmacological data to support the safety or efficacy of treatment below this age.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> The risk of severe or disseminated infection is very high, resulting in high morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Despite its severity, there are very few series in the literature on TB in newborns and young infants. The aim of our study was to describe the clinical characteristics, diagnostic methods, treatment and clinical course of patients under the age of 3 months diagnosed with TB at our centre.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Patients and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">The medical records of infants under the age of 3 months diagnosed with TB at the Hospital Universitario La Paz between 1 January 1978 and 31 December 2014 were reviewed. Clinical, epidemiological, radiological and microbiological data were collected, in addition to information about its clinical course and treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">A tuberculosis diagnosis was established in those infants who presented clinical, radiological and epidemiological data suggestive of TB, in addition to a culture or polymerase chain reaction (PCR) positive for <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> (MTB) in the patient or the proband (GeneXpert MTB/RIF®).</p><p id="par0030" class="elsevierStylePara elsevierViewall">A positive TST was deemed to be an induration ≥5<span class="elsevierStyleHsp" style=""></span>mm 48–72<span class="elsevierStyleHsp" style=""></span>h after the intradermal administration of 2<span class="elsevierStyleHsp" style=""></span>units/0.1<span class="elsevierStyleHsp" style=""></span>ml tuberculin RT-23 (Statens Serum Institute, Copenhagen, Denmark).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> An IGRA was performed on patients diagnosed after the year 2008. In each case, the QuantiFERON®-TB Gold In-Tube test (Cellestis Limited, Carnegie, Victoria, Australia) was used, in accordance with CDC guidelines.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Congenital TB was defined in accordance with the Cantwell criteria<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> of proved TB lesions and at least one of the following: symptoms in the first week of life; a primary hepatic complex or caseating hepatic granulomas; tuberculosis infection of the placenta or the maternal genital tract; or exclusion of the possibility of postnatal transmission by a thorough investigation of contacts.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The computer programme Excel (Microsoft, Redmond, USA) was used for data collection and analysis.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">555 cases of TB in children under the age of 14 years were diagnosed throughout the study period. Of these, 8 were in infants under the age of 3 months, representing 1.4% of all paediatric cases of TB.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The patients’ key characteristics are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Median age at diagnosis was 63 days (interquartile range 36–87 days). Five were children of Moroccan immigrants and 3 were of Spanish descent. Just one patient was asymptomatic and was diagnosed by means of a contact investigation. No epidemiological history of TB at the onset of symptoms was found in the other cases. TB was not suspected as an initial diagnosis in any of the patients (3 lower respiratory tract infections, 3 sepsis, 1 pertussis). The time between symptom onset and diagnosis in these cases ranged from 2 to 6 weeks.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Two infants initially presented a negative TST, which turned positive when repeated 8 weeks later. The QuantiFERON®-TB Gold In-Tube test was performed in 3 cases, with 1 positive result and 2 inconclusive due to a lack of lymphocyte activation in the positive or mitogen control tube. Three cases were found positive by PCR for MTB in gastric juice or bronchial aspirate. A resistance study was conducted in 6 patients without isolating any resistant strain. Case 1 died from respiratory failure refractory to treatment in the first 24<span class="elsevierStyleHsp" style=""></span>h of hospitalisation and the diagnosis was confirmed post-mortem. For the other 7 patients, median hospitalisation time was 33 days (interquartile range 17–132 days). They all received standard treatment that was well tolerated: isoniazid, rifampicin, pyrazinamide and an aminoglycoside (streptomycin or amikacin) for 2 months, followed by isoniazid or rifampicin for 7 months in cases of pulmonary involvement only, and 10 months for the 2 patients with miliary dissemination. No patient presented pharmacological toxicity. All progressed favourably with no meningeal involvement or sequelae.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In terms of disease acquisition, postnatal transmission from a cohabiting adult with TB was confirmed in 2 patients (cases 5 and 8). A further 3 infants (cases 1, 6 and 7) met the congenital TB criteria. In case 1, MTB was isolated from lung and liver samples obtained from the autopsy. After the death of the patient, the mother developed disseminated TB with meningeal involvement. In patients 6 and 7, the contact investigation revealed maternal genital tuberculosis by endometrial biopsy (granulomatous endometritis and PCR positive for MTB). Cases 2, 3 and 4 were highly suggestive of congenital TB having failed to identify a proband with TB in the contact investigation. The 3 mothers presented a positive TST with normal chest X-ray, and one had a history of recurrent miscarriage. However, as an endometrial biopsy or an anatomopathological study of the placenta were not performed, maternal genital TB could not be proven.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">TB is a rare, but potentially very serious, condition in infants under the age of 3 months. Its aggressive clinical course has been associated with the immaturity of the immune system, weak initial clinical suspicion and delayed diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,4</span></a> It is estimated that between 10% and 20% of untreated infants with TB develop meningitis or miliary dissemination.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> The development of severe infection is even more common in untreated neonatal TB, with a mortality rate of almost 100%, particularly congenital forms of the disease.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> It is particularly important to suspect a TB diagnosis in the absence of known epidemiological history. Symptoms of neonatal TB are nonspecific, and the patient may be afebrile.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> For this reason, TB should be considered in the differential diagnosis of infants under the age of 3 months with sepsis or pneumonia with negative bacterial cultures and an unfavourable clinical course, or in patients with longstanding pertussis without lymphocytosis, especially if their mothers come from regions of high TB endemicity.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Radiological abnormalities are typical in this age group. Lymphadenopathies and miliary pattern are frequently found, although interstitial, nodular and even cavitated forms have also been reported.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10,11</span></a> Although none of our patients had meningitis, this must always be ruled out as it has been reported in 11–22% of children.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In terms of diagnostic techniques, TST was positive in 5 out of 7 patients (71%), although the literature reports a reactivity rate of less than 20%.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9,10</span></a> The delayed diagnosis of our patients probably contributed to this high positive test rate. The 2 patients with an initial negative TST were later found to be positive with the same test, which highlights its diagnostic value and the need to repeat the test if tuberculosis is suspected. IGRA was performed in 3 cases, but aided diagnosis in just 1 patient. There is very little information in the literature concerning the effectiveness of these techniques in infants, but they seem to offer lower sensitivity and a higher rate of inconclusive results than in older children.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">12,13</span></a> The effectiveness of microbiological studies, on the other hand, is high.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Our series comprised 3 confirmed cases of congenital tuberculosis, 3 suspected cases and just 2 postnatal tuberculosis cases, despite the fact that TB acquired after birth is considered to be more common.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> None of the mothers of infants with congenital TB was diagnosed during pregnancy. This situation can arise if the mother develops symptoms post-partum or has genital TB, owing to the lack, or nonspecificity, of symptoms. For this reason, an endometrial biopsy is recommended in newborns with TB if the mother presents a positive TST, normal chest X-ray and negative family history.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">7,11</span></a> This is particularly important in children of immigrants from countries of high tuberculosis endemicity conceived by <span class="elsevierStyleItalic">in vitro</span> fertilisation, as genital TB is a common cause of tubal infertility.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Funding</span><p id="par0085" class="elsevierStylePara elsevierViewall">No funding was received to complete this work.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres827771" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec824085" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres827770" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec824086" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-01-02" "fechaAceptado" => "2015-03-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec824085" "palabras" => array:4 [ 0 => "Tuberculosis" 1 => "Congenital" 2 => "Infant" 3 => "Newborn" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec824086" "palabras" => array:4 [ 0 => "Tuberculosis" 1 => "Congénita" 2 => "Lactante" 3 => "Recién nacido" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A review was conducted on infants less than 3 months of age diagnosed with tuberculosis between 1978 and 2014. Eight patients were diagnosed (1.4% of paediatric tuberculosis cases): 3 confirmed congenital tuberculosis, 3 suspected (endometrial biopsy was not performed), and 2 postnatal tuberculosis. Tuberculin skin test was negative in two patients. Diagnostic performance of culture (7/7, 100%) and PCR (3/3, 100%) of gastric aspirates was higher than that of acid-fast bacilli smears (5/8, 62%) and IGRA test (1/3, 33%). Three patients developed miliary disease, and one died. In conclusion, tuberculosis in this age group is rare, severe, and difficult to diagnose. In cases lacking known postnatal contacts, maternal genital tuberculosis should be ruled out by endometrial biopsy.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Revisión de los lactantes menores de 3 meses con tuberculosis durante el periodo 1978-2014. Se diagnosticaron 8 casos (1,4% de las tuberculosis pediátricas): 3 tuberculosis congénitas, 3 sugestivas (biopsia endometrial no realizada) y 2 posnatales. La prueba de tuberculina fue negativa en 2 casos. La rentabilidad diagnóstica del cultivo (7/7, 100%) o PCR (3/3, 100%) de aspirado gástrico fue superior a la de la baciloscopia (5/8, 62%) y el test IGRA (1/3, 33%). Tres pacientes presentaron diseminación miliar y uno falleció. En conclusión, la tuberculosis en este grupo de edad es infrecuente, grave y de difícil diagnóstico. En ausencia de contactos posnatales conocidos, se recomienda descartar tuberculosis genital materna mediante biopsia endometrial.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: del Rosal Rabes T, Baquero-Artigao F, Méndez-Echevarría AM, Mellado Peña MJ. Tuberculosis en lactantes menores de 3 meses. Enferm Infecc Microbiol Clin. 2017;35:243–245.</p>" ] ] "multimedia" => array:1 [ 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: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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Year \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (days) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Preterm \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Initial symptoms \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tuberculin skin test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Chest X-ray \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sputum smear microscopy \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Culture (sample) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Corticosteroids \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Proband \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1978 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cough, breathing difficulties, food refusal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not conducted due to death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Miliary pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive in autopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not performed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1986 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever, breathing difficulties \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hilar adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(gastric aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1992 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever, cough \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hilar adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(gastric aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1998 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pertussis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Miliary pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(gastric aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever, cough \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1° 0<span class="elsevierStyleHsp" style=""></span>mm<br>2° 10<span class="elsevierStyleHsp" style=""></span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hilar adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(gastric aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Brother (17 years) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pertussis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hilar adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(gastric aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever, breathing difficulties \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1° 0<span class="elsevierStyleHsp" style=""></span>mm<br>2° 8<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Miliary pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(tracheal aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asymptomatic (contact investigation) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6<span class="elsevierStyleHsp" style=""></span>mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal.<br>CT: lymphadenopathies and infiltrates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive<br>(gastric aspirate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cousin (29 years) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1392781.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics of infants under the age of 3 months with tuberculosis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Perinatal tuberculosis: new challenges in the diagnosis and treatment of tuberculosis in infants and the newborn" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 0 | 6 |
| 2024 October | 214 | 14 | 228 |
| 2024 September | 245 | 14 | 259 |
| 2024 August | 252 | 36 | 288 |
| 2024 July | 287 | 22 | 309 |
| 2024 June | 203 | 5 | 208 |
| 2024 May | 216 | 3 | 219 |
| 2024 April | 232 | 7 | 239 |
| 2024 March | 320 | 14 | 334 |
| 2024 February | 248 | 11 | 259 |
| 2024 January | 285 | 15 | 300 |
| 2023 December | 209 | 9 | 218 |
| 2023 November | 266 | 16 | 282 |
| 2023 October | 256 | 21 | 277 |
| 2023 September | 174 | 11 | 185 |
| 2023 August | 181 | 7 | 188 |
| 2023 July | 124 | 12 | 136 |
| 2023 June | 124 | 10 | 134 |
| 2023 May | 123 | 10 | 133 |
| 2023 April | 84 | 2 | 86 |
| 2023 March | 113 | 13 | 126 |
| 2023 February | 70 | 6 | 76 |
| 2023 January | 64 | 9 | 73 |
| 2022 December | 67 | 10 | 77 |
| 2022 November | 82 | 13 | 95 |
| 2022 October | 54 | 9 | 63 |
| 2022 September | 52 | 13 | 65 |
| 2022 August | 28 | 12 | 40 |
| 2022 July | 9 | 7 | 16 |
| 2022 June | 16 | 7 | 23 |
| 2022 May | 18 | 9 | 27 |
| 2022 April | 32 | 12 | 44 |
| 2022 March | 27 | 11 | 38 |
| 2022 February | 18 | 4 | 22 |
| 2022 January | 43 | 5 | 48 |
| 2021 December | 12 | 10 | 22 |
| 2021 November | 9 | 7 | 16 |
| 2021 October | 28 | 7 | 35 |
| 2021 September | 28 | 8 | 36 |
| 2021 August | 43 | 7 | 50 |
| 2021 July | 10 | 9 | 19 |
| 2021 June | 11 | 10 | 21 |
| 2021 May | 17 | 10 | 27 |
| 2021 April | 19 | 22 | 41 |
| 2021 March | 12 | 9 | 21 |
| 2021 February | 10 | 7 | 17 |
| 2021 January | 17 | 12 | 29 |
| 2020 December | 14 | 9 | 23 |
| 2020 November | 9 | 8 | 17 |
| 2020 October | 9 | 7 | 16 |
| 2020 September | 14 | 32 | 46 |
| 2020 August | 8 | 27 | 35 |
| 2020 July | 8 | 7 | 15 |
| 2020 June | 10 | 7 | 17 |
| 2020 May | 16 | 17 | 33 |
| 2020 April | 9 | 10 | 19 |
| 2020 March | 10 | 4 | 14 |
| 2020 February | 6 | 2 | 8 |
| 2020 January | 9 | 9 | 18 |
| 2019 December | 18 | 10 | 28 |
| 2019 November | 8 | 8 | 16 |
| 2019 October | 7 | 3 | 10 |
| 2019 September | 10 | 6 | 16 |
| 2019 August | 3 | 0 | 3 |
| 2019 July | 12 | 6 | 18 |
| 2019 June | 35 | 17 | 52 |
| 2019 May | 142 | 29 | 171 |
| 2019 April | 66 | 14 | 80 |
| 2019 March | 7 | 5 | 12 |
| 2019 February | 4 | 7 | 11 |
| 2019 January | 4 | 3 | 7 |
| 2018 December | 0 | 2 | 2 |
| 2018 November | 7 | 10 | 17 |
| 2018 October | 8 | 5 | 13 |
| 2018 September | 7 | 7 | 14 |
| 2018 August | 8 | 3 | 11 |
| 2018 July | 13 | 0 | 13 |
| 2018 June | 7 | 1 | 8 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 4 | 3 | 7 |
| 2018 March | 3 | 0 | 3 |
| 2018 February | 4 | 0 | 4 |
| 2018 January | 9 | 1 | 10 |
| 2017 December | 3 | 0 | 3 |
| 2017 November | 10 | 0 | 10 |
| 2017 October | 8 | 2 | 10 |
| 2017 September | 2 | 0 | 2 |
| 2017 May | 2 | 0 | 2 |
| 2017 March | 0 | 1 | 1 |
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