Guidelines for the prevention and control of tuberculosis in health care workers

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IGRA: técnicas in vitro de interferón-gamma; H: isoniazida; PT: prueba de la tuberculina; Rx: radiografía; TB: tuberculosis; TIT: tratamiento de la infección latente; TITP: tratamiento de la infección tuberculosa probable." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Irma Casas, Jose Dominguez, Soledad Rodríguez, Joan Matllo, Neus Altet" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Irma" "apellidos" => "Casas" ] 1 => array:2 [ "nombre" => "Jose" "apellidos" => "Dominguez" ] 2 => array:2 [ "nombre" => "Soledad" "apellidos" => "Rodríguez" ] 3 => array:2 [ "nombre" => "Joan" "apellidos" => "Matllo" ] 4 => array:2 [ "nombre" => "Neus" "apellidos" => "Altet" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020616300432" "doi" => "10.1016/j.medcle.2016.04.021" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616300432?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315004467?idApp=UINPBA00004N" "url" => "/00257753/0000014500000012/v1_201512060029/S0025775315004467/v1_201512060029/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020616300444" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.04.022" "estado" => "S300" "fechaPublicacion" => "2015-12-21" "aid" => "3328" "copyright" => "Elsevier España, S.L.U." 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"autores" => array:5 [ 0 => array:3 [ "nombre" => "Irma" "apellidos" => "Casas" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "Jose" "apellidos" => "Dominguez" "email" => array:1 [ 0 => "jadomb@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Soledad" "apellidos" => "Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 3 => array:3 [ "nombre" => "Joan" "apellidos" => "Matllo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] 4 => array:3 [ "nombre" => "Neus" "apellidos" => "Altet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Preventiva, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Microbiología, Institut d’Investigació Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Prevención de Riesgos Laborales, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat , Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Prevención de Riesgos Laborales, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Unitat de Prevenció i Control de la Tuberculosi de Barcelona, Barcelona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Guía para la prevención y control de la tuberculosis en el personal sanitario" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2635 "Ancho" => 2654 "Tamanyo" => 331107 ] ] "descripcion" => array:1 [ "en" => "Performance on contact study jointly considering the results of the TST and IGRA. IGRA: in vitro interferon-gamma release assays; TST: Tuberculin test; Rx: X-ray; TB: tuberculosis; LTBI: treatment for latent TB infection; TPTI: treatment of probable tuberulosis infection." ] ] ] "textoCompleto" => "Introduction and methodologyTuberculosis (TB) remains today one of the infectious diseases with highest global morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0240">1,2</a> The species grouped in Mycobacterium tuberculosis (M. tuberculosis) complex are the causative agents of TB. The main reservoir is infected human being and the source of infection the sick person, especially a person with cough, pulmonary cavitary lesion and acid-alcohol resistant bacilli (AARB) in sputum. The most important route of transmission is air, by contaminated aerosols coming from the breath of sick people, which have the ability to remain suspended in the ambient air. We should also consider the transmission in laboratories handling contaminated biological samples.<a class="elsevierStyleCrossRef" href="#bib0250">3</a>The most common form of the disease is in the lung, whereas 20–40% of cases have an extrapulmonary or mixed location (miliary, lymph nodes, genitourinary, osteoarticular, or meningeal).In Europe, TB remains a major public health problem. In 2010, 388,875 cases of TB were reported in 52 countries in Europe (incidence rate of 43.2 per 100,000 population), with significant variability among different countries.<a class="elsevierStyleCrossRef" href="#bib0255">4</a> This region contains about 4.7% of all cases detected worldwide. Notification of the countries of the European Union and the European Economic Area follows a downward trend with a 4% average rate. Spain, with a rate of 13.04 cases per 100,000 population in 2012, continues to have gross rates above the average of the countries of the European Union and the European Economic Area with a significant variability among the autonomous communities, ranging from 6.5 cases per 100,000 in the Canary Islands, to 24.6 cases per 105 in Galicia.<a class="elsevierStyleCrossRef" href="#bib0260">5</a>In this scenario, healthcare providers (HCP) working in a center where patients are treated for TB may be exposed to this occupational hazard. Healthcare providers have reported in our environment high incidence of tuberculosis infection (15.4% at 4 years of follow-up) although there has been a downward trend in recent years.<a class="elsevierStyleCrossRef" href="#bib0265">6</a> A systematic review in middle and low income countries estimated annual risk of tuberculosis infection ranging from 3.9 to 14.3%.<a class="elsevierStyleCrossRef" href="#bib0270">7</a> Similarly, the incidence of tuberculosis in healthcare providers has been declining in recent years, but there is still high occupational risk of TB in these professionals.<a class="elsevierStyleCrossRefs" href="#bib0275">8–10</a> In another systematic review it was estimated that the annual risk of developing TB was 3 times higher in the healthcare providers compared to the general population.<a class="elsevierStyleCrossRef" href="#bib0275">8</a> This risk is not the same in all working areas or units, being highest in emergency rooms, microbiology and pathology laboratories, as well as in units where certain procedures such as sputum induction or bronchoscopies are performed.<a class="elsevierStyleCrossRef" href="#bib0285">10</a>In order to reduce this risk it is important to be provided with measures of infection control in healthcare providers. One of the most important measures is the training of health personnel in the early diagnosis of patients with TB, as well as respiratory isolation measures and the use of respirators. Another important measure is to monitor health personnel regularly by screening techniques for tuberculosis infection. The health personnel screening should be performed for 2 main reasons. One purpose is to prevent the transmission from healthcare providers to patients by detecting early TB cases in health personnel. A second purpose is to detect and treat early TB infection in healthcare providers in order to prevent the development of the disease.<a class="elsevierStyleCrossRef" href="#bib0290">11</a>The existing national guidelines currently include the tuberculin skin test (TST) as a screening test for TB infection, referring to interferon gamma release assays (IGRA) for a number of cases.<a class="elsevierStyleCrossRefs" href="#bib0295">12–14</a> This guideline was an initiative of the Institut Català de la Salut based on evidence available today. Its purpose has been to reach a consensus and establish common criteria to include IGRA assays as an additional aid to the TST in healthcare providers. The recommendations of use have been adapted to different situations: screening of infection in healthcare providers, both at the time of incorporation at work and periodically. Performance when tuberculosis is suspected in healthcare providers; and performance against accidental exposure to a patient with TB or material potentially infected. Subsequently, the invitation was extended to involve various medical and scientific societies of our country.In short, this guideline aims to be a tool that allows the professionals involved in monitoring the health of health professionals to address, efficiently, the study not only of tuberculosis, but also of tuberculous infection in healthcare.This guidelines has been divided into several sections:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Diagnosis of infection and/or tuberculosis disease</li><li class="elsevierStyleListItem" id="lsti0010">2.Screening for tuberculosis infection in healthcare providers</li><li class="elsevierStyleListItem" id="lsti0015">3.Performance against accidental exposure to a patient with active TB</li><li class="elsevierStyleListItem" id="lsti0020">4.Performance of Prevention Department against cases of TB or suspected TB in healthcare providers</li><li class="elsevierStyleListItem" id="lsti0025">5.Occupational aptitude criteria</li><li class="elsevierStyleListItem" id="lsti0030">6.General preventive measures</li><li class="elsevierStyleListItem" id="lsti0035">7.Preventive measures in healthcare providers specially susceptible</li><li class="elsevierStyleListItem" id="lsti0040">8.Preventive measures in pregnancy and lactation</li></ul>This guideline is supported by the following companies and scientific organizations: Spanish Society of Pneumology and Thoracic Surgery (SEPAR), Study Group on mycobacterial infections (GEIM) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Spanish Association of Specialists in Occupational Medicine (AEEMT) and Program on prevention and control of TB of the Public Health Agency of Catalonia.Diagnosis of infection and/or tuberculosis diseaseThe information in order to establish the diagnosis of infection and/or tuberculosis should be obtained through:Occupational hazard assessmentIt will take place in every workplace and will be performed by the risk prevention technical staff<a class="elsevierStyleCrossRefs" href="#bib0290">11,15,16</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, risk areas).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>AnamnesisSpecific anamnesis is required to investigate personal and family history of tuberculosis, previous TST and/or IGRA with investigation, if necessary, of the state of infection, previous treatment with anti-TB drugs and previous BCG vaccination. It is considered that a person has been vaccinated with BCG if they have the typical scar and/or provide the vaccination card proving it. It should also be aimed at identifying risk groups both in TB infection and progression to TB disease<a class="elsevierStyleCrossRefs" href="#bib0305">14,17,18</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Specific clinical examinationIt should be aimed at detecting clinical features that can increase the probability of TB acquisition and/or transmission, and detecting the symptoms and signs of this disease.Additional examinationsTuberculin skin test<a class="elsevierStyleCrossRef" href="#bib0330">19</a>All healthcare providers should undergo this test when recruited, and serially, to those at risk for TB infection, except for those providing documentation proving previous positive results consistent with TB infection or who have suffered TB. The procedure of performing and reading the TST is specified in <a class="elsevierStyleCrossRef" href="#sec0175">Annex I</a>. Because of the difficulty to interpret the results, booster effect is not recommended. Thus, a technical IGRA is required to prevent it.Interferon-gamma in vitro assaysThey are based on the interferon-gamma detection (IFN-γ) released in response to in vitro stimulation of sensitized T cells present in peripheral blood with M. tuberculosis specific antigens. The amount of IFN-γ produced can be measured (QuantiFERON®-Gold-In tube; QIAGEN, Düsseldorf, Germany) as well as the number of mononuclear cells producing it through specific stimulation (T-SPOT.TB®; Oxford Immunotec, Oxford, United Kingdom). QuantiFERON®-Gold-In tube uses specific antigens of M. tuberculosis (ESAT-6, CFP-10 y TB7.7), but T-SPOT.TB®, stimulated with ESAT-6 y CFP-10, is generally considered to be more sensitive since it obtains more positive results.<a class="elsevierStyleCrossRefs" href="#bib0335">20,21</a>Chest X-rayIf TST and/or IGRA are positive, tuberculosis should be excluded through a radiological study. It should also be performed in the healthcare providers with a negative TST or IGRA, but with comorbidities causing immunosuppression.Other testsIf tuberculosis is suspected, always according to the strict indication of the medical staff, bacteriological analysis and other diagnostic tests can be performed until obtaining disease confirmation or exclusion.Screening for tuberculosis infection in healthcare providersThe TST and/or IGRA, as baseline screening, are recommended in subjects working in the healthcare system, regardless of the risk associated with their job. In general, neither TST nor the IGRA are to be used to investigate periodically people at low risk of tuberculosis infection or disease. Therefore, it is important to classify the healthcare providers according to the occupational risk of infection and their personal risk of disease if infected.Healthcare providers are considered to have a positive TST if induration is not below 5mm.<a class="elsevierStyleCrossRef" href="#bib0305">14</a> It should be noted that BCG does not prevent TB infection and, therefore, the TSTs ranging 5–14mm may be due to either tuberculous infection or BCG vaccination or nontuberculous mycobacteria. The more time has elapsed since vaccination (15 years or more) and the larger the diameter of the TST induration, the higher the probability that the reaction is due to TB infection.<a class="elsevierStyleCrossRef" href="#bib0345">22</a> In studies of high-risk-infection contacts and workers (HIV infected, immunosuppressive therapy or symptoms suggesting TB), history of vaccination must not be taken into account and TST will be considered positive if it is equal or above 5mm.<a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a> shows the interpreting criteria of T-SPOT.TB and QuantiFERON®-Gold-In tube.<a class="elsevierStyleCrossRef" href="#bib0350">23</a> If IGRA are “indeterminate” they should be repeated to confirm the result, and evaluate the possibility of a potential technical error or immunosuppression.IGRA have shown a good correlation with risk factors of exposure to TB in places of low incidence of the disease. But their use in serial screening of healthcare providers show significant intraindividual variation, with high conversion and reversal rates.<a class="elsevierStyleCrossRefs" href="#bib0355">24–26</a> This is because the optimal performance thresholds for test conversion and reversal have not been well defined yet. To prevent false conversions and reversals in the serial study, it has been defined an area of uncertainty where the result must be considered limit (<a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a>) and the test requires to be repeated to verify the result.<a class="elsevierStyleCrossRefs" href="#bib0350">23,27</a>The use of IGRA instead of the TST as the sole screening test produces a lower prevalence of positive tests and, therefore, the number of health workers who receive unnecessary treatment for TB infection will decrease. It also has important advantages over the TST, such as preventing the booster effect as well as logistic advantages for being an in vitro test: confidentiality, it is not necessary a second visit, and its interpretation is more objective than TST. Consequently, in the case of health workers with a negative TST, serial screening test can still be performed with the TST. If tuberculin conversion is detected, IGRA is recommended. To decide the therapeutic action it is necessary to evaluate important factors, such as: contact with TB case, personal risk factors, BCG vaccination, history of previous TST and date, induration intensity and other diagnostic information.<a class="elsevierStyleCrossRefs" href="#bib0320">17,18</a>Regular monitoring, once the healthcare providers already have a positive TST but negative IGRA, should be performed through IGRA.In centers where IGRA is not available, monitoring will continue to be performed with the TST.The recommendations of joint use of TST and IGRA are presented according to the initial results of the TST, as follows:If healthcare providers already have a previous positive tuberculin testIGRA determination is recommended to have a baseline result. This information may be important to assess the performance against a potential occupational exposure of these workers to TB patients.If healthcare providers already have a previous negative tuberculin testIn the case of health workers with a previous negative TST, they should undergo another TST and proceed in accordance with <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>If healthcare providers do not have a previous tuberculin test or the result is unknownIf healthcare providers do not have a previous tuberculin test or the result is unknown, a new TST is required and it should be proceeded in accordance with <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>All staff with a positive result of TST and/or IGRA should undergo a simple chest X-ray and anamnesis in order to dismiss active TB disease. If dismissed, it is considered that the person has TB infection. For the purposes of subsequent risk of developing TB disease and its management, the following different situations should be considered:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0045">•Recent TB infection or tuberculin conversion: when the worker's TST and/or IGRA has been positivized in less than 2 years.</li><li class="elsevierStyleListItem" id="lsti0050">•Tuberculous infection without conversion criteria: a worker shall be deemed to have tuberculous infection without conversion criteria when the TST and/or IGRA has been positivized in over two years.</li></ul>Frequency of monitoringExposure to TB patients is an occupational risk factor for healthcare professionals. All personnel newly recruited should undergo specific monitoring, compulsorily. Regular monitoring of health workers who have negative results at baseline screening is necessary in order to detect their risk to exposure. This requirement is based on the classification of the risk of TB transmission in the workplace and the risk of healthcare workers of developing the disease if infected with the TB bacillus. Periodically it should be assessed whether a given workplace has the same transmission risk or it has changed, and if the medical staff has the same risk of disease, if infected.Groups with no high risk of TB infection or disease need not be screened routinely to optimize resources.Performance against accidental exposure to a patient with active tuberculosisIf an accidental occupational exposure to a patient with active TB occurs, we should proceed to monitor the state of all staff in contact with the case. Accidental exposure is the contact with a TB patient not having taken the right measures of air isolation. The main cause of accidental exposure is the delayed diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0375">28,29</a>The criteria for deciding whether or not a worker should be tested, will be applied based on the time of contact with the source and degree of infectiousness of the patient, as well as the degree of immunosuppression of the exposed person.The investigations carried out and measures taken must be recorded in the medical history of the healthcare providers.The actions to be taken in this research are as follows:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055">1.Index case (IC) data collection: the person infected with TB has to be evaluated (clinical symptoms and delayed diagnosis, type of injury, microbiological study of sputum), which is related to the ability of the patient to aerosolize bacilli and the number of bacilli that are aerosolized.<a class="elsevierStyleCrossRefs" href="#bib0385">30,31</a> Practically, any patient in which the M. tuberculosis has been isolated from a respiratory sample other than that of a biopsy can be described as potential TB bacillus transmitter. The smear-positive patient is the major transmitter of the disease. The higher levels of bacilli, the more infectiousness. If the smear is negative but culture is positive, even though the patient can transmit the disease, the degree of infectiousness is lower. Patients with cough and cavitation on chest X-ray are the most infectious. In addition, the more days have elapsed until air isolation measures have been established for the patient, the higher risk of transmission.</li><li class="elsevierStyleListItem" id="lsti0060">2.Registration of personnel exposed: The person in charge is the assisting person.</li><li class="elsevierStyleListItem" id="lsti0065">3.Personnel exposed: assessment of the degree of exposure to the case (time of exposure, frequency and risk tasks or techniques). The risk tasks or techniques are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<a class="elsevierStyleCrossRef" href="#bib0295">12</a> Concentric circles, being HCP investigation a priority with a cumulative exposure of 8h if the case is bacilliferous, or 40h if the smear is negative but the sputum culture is positive.<a class="elsevierStyleCrossRef" href="#bib0395">32</a> The immunosuppressed HCP and HCP with sporadic contact but having performed risk tasks or techniques to the case without the proper respiratory protection measures will also be deemed as a priority. The diagnostic evaluation and therapeutic approach are determined in <a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0070">4.Notification of accidental exposures such as work accidents without a sick leave: to the Mutua de Accidentes de Trabajo y Enfermedades Profesionales (Mutual of Accidents and Occupational Diseases).</li><li class="elsevierStyleListItem" id="lsti0075">5.Verify compliance with the protocols to prevent future accidental exposures.<a class="elsevierStyleCrossRef" href="#bib0380">29</a></li></ul><a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a> show the algorithm against occupational exposure to active TB cases according to the result of the TST and IGRA. In this case, TST is considered positive when induration ≥5mm and ≥6mm increase if baseline TST was negative. IGRAs are considered positive or negative as described in <a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a>. In the study of accidental exposure, limit results should be considered as positive.Performance of the Prevention Department against cases of TB or suspected TB in healthcare providersIf it is detected that the worker has a clinical symptomatology consistent with TB disease or TB already confirmed, 2 types of investigation should be initiated:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080">a)Conventional investigation of contacts: aimed at contacts of healthcare providers in order to investigate whether or not there transmission of infection has occurred. The study of occupational contacts will be the responsibility of the Prevention Department. Non-occupational contacts (family, community and patients) will be the responsibility of the Units of Epidemiological Surveillance and welfare centers. Patients in contact with the medical staff should be checked up to find the possible source of infection (although non-occupational transmission cannot be ruled out) or possible cases of transmission.<a class="elsevierStyleCrossRef" href="#bib0400">33</a></li><li class="elsevierStyleListItem" id="lsti0085">b)It should also be reviewed whether or not the protocols to prevent transmission of tuberculosis infection have been correctly completed.</li></ul>The infectivity of healthcare providers infected with TB should be evaluated (clinical symptoms and delayed diagnosis, type of injury, microbiological study of sputum), which is related to the ability of the patient to aerosolize the bacilli and the number of bacilli that are aerosolized. Practically, any person to whom M. tuberculosis has been isolated from a respiratory specimen other than from a biopsy can be defined as a potential transmitter of tubercle bacilli.Period of infectiousnessDelayed diagnosis is a determining factor for the period of infectiousness of a patient. The onset of infectiousness cannot be determined objectively. The onset of cough is usually used as the time when the transmission begins; in the absence of cough, the onset of any respiratory symptoms attributable to TB.To determine the period of infectiousness during which contacts have been exposed and which should be investigated within the conventional contact study, the following rules can be used<a class="elsevierStyleCrossRef" href="#bib0405">34</a>:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0090">1)In an AARB patient, the period of infectivity begins 3 months before the collection of the first positive sample of sputum or from the onset of clinical symptoms.</li><li class="elsevierStyleListItem" id="lsti0095">2)Patients with 2 negative sputum samples (without AARB), but with positive culture can be deemed potentially infectious for a period of one month before the date of TB diagnosis.</li><li class="elsevierStyleListItem" id="lsti0100">3)Coughing or having cavitated lesions increases the degree of infectiousness.</li><li class="elsevierStyleListItem" id="lsti0105">4)The period of infectiousness of the disease sets the limits on contact investigation. By definition, in relation to the study of contacts, this period ends:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0110">a)At the time the relationship between the IC and the contact is ended.</li><li class="elsevierStyleListItem" id="lsti0115">b)When air isolation is established.</li><li class="elsevierStyleListItem" id="lsti0120">c)The date the first negative sputum sample is collected.</li></ul></li></ul>For practical purposes, it is considered that the patient is no longer infectious when has received adequate specific treatment for 15–21 days, there is clinical improvement and 3 negative sputum samples (without AARB) have been collected every other day.<a class="elsevierStyleCrossRefs" href="#bib0290">11,35</a>Risk of exposure and contact study prioritizationConventionally, contacts have been classified within “concentric circles” around the IC, taking into account infectiousness, the intensity and duration of exposure to IC and risk of disease of contact person, if infected. In each contact study, it should be specified which of these circles corresponds personnel exposure.<a class="elsevierStyleCrossRef" href="#bib0405">34</a> With the current evidence, the following considerations will be taken into account:First circle of contacts<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0125">a)Health personnel with 8h cumulative exposure to a bacilliferous IC or cumulative 40h if the smear is negative and the sputum culture is positive.</li><li class="elsevierStyleListItem" id="lsti0130">b)Health workers with some type of immunosuppression.</li></ul>Second circle of contactsHealth personnel with less than 8h cumulative exposure to a bacilliferous IC or less than cumulative 40h if the smear is negative and the sputum culture is positive.Third circle of contactsHealth workers with sporadic contact with the IC.Prioritization of the contact study begins with the first circle, followed by the second and then the third circle. But it is very important to consider that the risk of disease by a recent infection is high, as previously discussed. The priority of the contact rises from one circle to next when there are other risk factors. Therefore, the immunosuppressed patients of any etiology always belong to the first circle, even though their degree of contact is in the third circle.<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a> shows the evaluation algorithm and therapeutic approach to be followed in the study of the HPC contacts with TB, considering the joint use of the TST and IGRA.<elsevierMultimedia ident="fig0025"></elsevierMultimedia>In this case, TST is considered positive when induration ≥5mm and ≥6mm increase if baseline TST was negative. IGRAs are considered positive or negative according to <a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a>. In the study of contacts, the limit results should be considered as positive. Finally, it should be noted that if the TST was positive previously, patients should undergo IGRA.Occupational aptitude criteriaAny worker with pulmonary or airways TB have to be separated temporarily from their workplace for a minimum period of 2–3 weeks from the onset of specific treatment, taking into account the periods of infectiousness previously mentioned. The staff member should be reassessed before discharge and reintegration into the workplace.The infected staff, whether or not following treatment of tuberculosis infection (TTI), can continue to work, since it does not pose a risk to other people or patients.General preventive measuresCollective measuresMeasures must be applied in all centers treating patients with a diagnosis or suspected diagnosis of active respiratory TB.<a class="elsevierStyleCrossRefs" href="#bib0290">11,36,37</a>Administrative measures<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0135">•Identification, isolation, diagnosis and early treatment of patients with TB disease.</li><li class="elsevierStyleListItem" id="lsti0140">•Proper air isolation of patients with pulmonary or laryngeal TB<a class="elsevierStyleCrossRefs" href="#bib0410">35,38</a>: the person has to use surgical mask during transfers and while in waiting or common areas, and must follow proper respiratory hygiene. In primary care, if TB is suspected in a person coughing, this person should be provided with a surgical mask.</li><li class="elsevierStyleListItem" id="lsti0145">•The staff must have ongoing training regarding the signs and symptoms of TB, transmission mechanisms and prevention.</li></ul>Structural measures<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0150">•Patient's room: the room must be always individual and it should ideally be provided with a ventilation system with a powerful air extractor and negative pressure, with a renewed air every 6–12times/h. The air outlet to the outside must always be away from an air inlet or locations where there are other people. The door must always be closed, preferably by means of an automated system. The windows should be open as long as possible, and the room must be provided with an individual bathroom. If the air has to recirculate to other units of the hospital, HEPA filters are required.</li><li class="elsevierStyleListItem" id="lsti0155">•Medical waste: all waste containing respiratory secretions of the patient will be segregated in a bag that should be sealed, before leaving the room, and be treated as specific Group III medical waste.</li><li class="elsevierStyleListItem" id="lsti0160">•Mycobacteria laboratories: the facilities must be containment level 3 and separated from other laboratories. Access must be through a double door system. The laboratory must be provided with an airflow regulating system. All the air on its way out of the facilities must pass through the HEPA filters. They also have to be equipped with type 2 or 3 biological safety cabinets for handling infected samples and storing regular personal protective equipment.<a class="elsevierStyleCrossRef" href="#bib0430">39</a></li></ul>Individual measuresIndividual protection equipment<a class="elsevierStyleCrossRef" href="#bib0435">40</a>The staff will use high filtration mask, type FFP2, when in contact with a bacilliferous or suspected bacilliferous patient (room, etc.). The personnel responsible for pentamidine aerosolization, sputum induction, bronchoscopy, necropsy or alike, mycobacteria laboratories, handling urine of patients with TB or TB abscess drainage, must use a FFP3 protective mask. These masks are for personal use and replacement is recommended if they are dirty or damaged.Treatment of tuberculosis infectionIt is aimed at preventing the development of the disease in people who have been infected. Therefore, it is important to exclude the disease before starting the TTI. People at increased risk of developing the disease if infected, are described in the specific section regarding special susceptibility.<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0165">•Indications: treatment is indicated for all staff with a tuberculin conversion, regardless of age; in those with tuberculosis infection without conversion criteria but aged under 35; and workers with residual lesions consistent with TB never treated before. The person should be informed of the risks and benefits of treatment to ensure proper compliance.</li><li class="elsevierStyleListItem" id="lsti0170">•Treatment schedule: The duration of treatment is 6 months (minimum) to 12 months (optimal).<a class="elsevierStyleCrossRef" href="#bib0330">19</a> The treatment regimen with isoniazid (H) daily for 52 weeks, with over 80% compliance manages to prevent the development of the disease in more than 90% of patients.<a class="elsevierStyleCrossRef" href="#bib0440">41</a> But a very significant factor in the effectiveness of TTI is to get the patient to take the necessary doses of medication. Because it is difficult to obtain a proper compliance in long-term regimes, the 6-month regimen of H (6 H) is the most cost-effective schedule.<a class="elsevierStyleCrossRef" href="#bib0445">42</a> H intake should be in a single dose of 300mg/day and fasting. In cases of intolerance or resistance to H it is advisable to use rifampicin (R) for a period of 4 months (4 R).</li></ul>An alternative is to use the H+R regimen for 3 months (3 HR).<a class="elsevierStyleCrossRef" href="#bib0450">43</a> This regimen's efficacy (evidence) and toxicity are similar to that of 6 H, and compliance is best. Therefore, it should be deemed as an alternative regimen. It is an easy regimen, because both drugs are associated in marketed formulations.The use of R+pyrazinamide is not recommended for 2 months (2 RZ) due to its toxicity, although in people coinfected with HIV it is best tolerated.<a class="elsevierStyleCrossRef" href="#bib0455">44</a>In the absence of teratogenic effects caused by these drugs, they can be administered during pregnancy and lactation.<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0175">•Contraindications: history of adverse reactions to drugs used and decompensated acute or chronic liver disease.</li><li class="elsevierStyleListItem" id="lsti0180">•Follow-up: Before starting treatment, examination of liver function is recommended. Monitoring is performed basically to dismiss hepatotoxicity and other adverse effects and to enhance compliance with treatment through health education. Additional determination of liver function during the first 3–6 weeks of treatment is recommended. The treatment of infection should be discontinued if transaminase levels reach 3 times the upper limit of normal levels and patient has symptoms. Also if the level is 5 times over normal levels while the patient is asymptomatic.<a class="elsevierStyleCrossRefs" href="#bib0330">19,45</a></li></ul>Organizational measuresIf a recent or suspected TB infection or diagnosis of tuberculosis disease is detected, it will be reported to the technical area in order to review the risk assessment of the workplace and the corrective measures proposed. Notification to the local public health services of the medical center is compulsory.Pulmonary TB is an individualized disease, and must be reported promptly, as provided by the health authorities.Due to the emergence of the process in the workplace, it must be notified to the relevant MATEPSS as a professional contingency (occupational accident or disease) through the human resources management/unit of the center or area (RD1299/2006).<a class="elsevierStyleCrossRef" href="#bib0465">46</a>Preventive measures in special susceptibility workersThose workers particularly susceptible to the risk of TB should be identified and it should be assessed whether or not their job is a risk to their special susceptibility. Particularly susceptible circumstances are as follows:<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0185">•Immigration from countries with high incidence of TB. The risk of developing the disease is higher within the first 5 years since their arrival.</li><li class="elsevierStyleListItem" id="lsti0190">•Chronic renal failure.</li><li class="elsevierStyleListItem" id="lsti0195">•Immunodeficiencies.</li><li class="elsevierStyleListItem" id="lsti0200">•Silicosis.</li><li class="elsevierStyleListItem" id="lsti0205">•HIV infection.</li><li class="elsevierStyleListItem" id="lsti0210">•Diabetes mellitus.</li><li class="elsevierStyleListItem" id="lsti0215">•Long-term therapy with corticosteroids.</li><li class="elsevierStyleListItem" id="lsti0220">•Transplants.</li><li class="elsevierStyleListItem" id="lsti0225">•Immunosuppressive therapy (chemotherapy or anti-TNF).</li><li class="elsevierStyleListItem" id="lsti0230">•Chronic inflammatory disease or rheumatic diseases such rheumatoid arthritis.</li><li class="elsevierStyleListItem" id="lsti0235">•Leukemias, lymphomas and other neoplastic processes.</li><li class="elsevierStyleListItem" id="lsti0240">•Gastrectomy and intestinal bypass.</li><li class="elsevierStyleListItem" id="lsti0245">•A history of drug dependence.</li></ul>Preventive measures in pregnancy and lactationPregnancy is not considered a situation of special susceptibility, since for most of working females the risk of infection is not higher than in the general population. However, the following should be taken into account<a class="elsevierStyleCrossRefs" href="#bib0295">12,47</a>:<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0250">•There is no evidence that the TST has adverse effects on pregnant women or the fetus, but it should only be performed if there are risk factors for infection and progression to TB disease.</li><li class="elsevierStyleListItem" id="lsti0255">•Pregnancy does not increase the risk of developing the disease. Thus, in the case of diagnosing TB infection, it is recommended that the TTI be postponed. It is advisable to start after 2–3 weeks postpartum to prevent potential hepatotoxicity of H in the immediate postpartum period.<a class="elsevierStyleCrossRef" href="#bib0405">34</a></li><li class="elsevierStyleListItem" id="lsti0260">•TTI is recommended in women at high risk of progression from infection to tuberculosis (recently infected women or women coinfected with HIV). In these cases the initiation of treatment need not be delayed, even if in the first quarter of pregnancy.</li><li class="elsevierStyleListItem" id="lsti0265">•The treatment of choice in the TTI is the 6 H regimen (with pyridoxine supplements).</li><li class="elsevierStyleListItem" id="lsti0270">•Breastfeeding is not contraindicated if the mother is following TTI, because even though drugs are excreted in human milk, they do so in very small concentrations as to produce adverse effects on the infant.</li><li class="elsevierStyleListItem" id="lsti0275">•If TB disease has been diagnosed during pregnancy, treatment should not be delayed because untreated TB means higher risk for both pregnant woman and fetus.</li></ul>Conflict of interestsThe authors report no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres635244" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec647754" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres635245" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec647753" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction and methodology" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Diagnosis of infection and/or tuberculosis disease" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Occupational hazard assessment" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Anamnesis" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Specific clinical examination" ] 3 => array:3 [ "identificador" => "sec0030" "titulo" => "Additional examinations" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Tuberculin skin test" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Interferon-gamma in vitro assays" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Chest X-ray" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Other tests" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0055" "titulo" => "Screening for tuberculosis infection in healthcare providers" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "If healthcare providers already have a previous positive tuberculin test" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "If healthcare providers already have a previous negative tuberculin test" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "If healthcare providers do not have a previous tuberculin test or the result is unknown" ] 3 => array:2 [ "identificador" => "sec0075" "titulo" => "Frequency of monitoring" ] ] ] 7 => array:2 [ "identificador" => "sec0080" "titulo" => "Performance against accidental exposure to a patient with active tuberculosis" ] 8 => array:3 [ "identificador" => "sec0085" "titulo" => "Performance of the Prevention Department against cases of TB or suspected TB in healthcare providers" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Period of infectiousness" ] 1 => array:3 [ "identificador" => "sec0095" "titulo" => "Risk of exposure and contact study prioritization" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "First circle of contacts" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Second circle of contacts" ] 2 => array:2 [ "identificador" => "sec0110" "titulo" => "Third circle of contacts" ] ] ] ] ] 9 => array:2 [ "identificador" => "sec0115" "titulo" => "Occupational aptitude criteria" ] 10 => array:3 [ "identificador" => "sec0120" "titulo" => "General preventive measures" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0125" "titulo" => "Collective measures" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0130" "titulo" => "Administrative measures" ] 1 => array:2 [ "identificador" => "sec0135" "titulo" => "Structural measures" ] ] ] 1 => array:3 [ "identificador" => "sec0140" "titulo" => "Individual measures" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0145" "titulo" => "Individual protection equipment" ] 1 => array:2 [ "identificador" => "sec0150" "titulo" => "Treatment of tuberculosis infection" ] ] ] 2 => array:2 [ "identificador" => "sec0155" "titulo" => "Organizational measures" ] ] ] 11 => array:2 [ "identificador" => "sec0160" "titulo" => "Preventive measures in special susceptibility workers" ] 12 => array:2 [ "identificador" => "sec0165" "titulo" => "Preventive measures in pregnancy and lactation" ] 13 => array:2 [ "identificador" => "sec0170" "titulo" => "Conflict of interests" ] 14 => array:2 [ "identificador" => "xack214072" "titulo" => "Acknowledgements" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-10-14" "fechaAceptado" => "2015-06-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec647754" "palabras" => array:3 [ 0 => "Tuberculosis" 1 => "Health care workers" 2 => "Gamma interferon" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec647753" "palabras" => array:3 [ 0 => "Tuberculosis" 1 => "Personal sanitario" 2 => "Interferón-gamma" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Tuberculosis remains one of the communicable diseases that cause increased morbidity and mortality worldwide. With an incidence rate of 13.04 per 100,000 population, Spain ranks third among the most affected European countries. These data show a tendency to decrease meaning that it may go unnoticed with the potential to miss the appropriate preventive measures in a suspected case. In centers where patients are treated with tuberculosis, health care worker presents risk of transmission. This risk is higher in some areas or work units. The occupational health physicians’ services, which monitorize the health of health care workers, use different strategies in order to prevent and detect tuberculosis infection. The national guidelines include the tuberculin skin test as a screening test for tuberculosis infection with mention of new diagnostic tests based on the in vitro detection of gamma interferon (IGRA) for certain cases. The purpose of this guide is to establish common criteria for IGRA tests, as a supplementary aid to the tuberculin skin test in health care workers, from the evidence available today. Recommendations for its use have been adapted to the different situations faced by the professionals involved in monitoring the health of health workers." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La tuberculosis continúa siendo una de las enfermedades transmisibles causantes de mayor morbimortalidad en el mundo. España con una tasa de incidencia de 13.04 por 100.000 habitantes ocupa el tercer lugar entre los países europeos más afectados. Estos datos muestran una tendencia a su disminución, pudiendo pasar desapercibida y hacer que no se realicen las medidas de prevención adecuadas ante un enfermo sospechoso. El personal sanitario que trabaja en un centro donde se atiende a pacientes con tuberculosis presenta riesgo de transmisión, siendo este riesgo superior en determinadas áreas o unidades de trabajo. Desde los Servicios de Prevención de Riesgos Laborales, encargados de vigilar la salud de los trabajadores sanitarios, se elaboran diferentes estrategias de abordaje con el objetivo de evitar la infección en estos trabajadores y detectar la infección tuberculosa reciente. Las guías nacionales existentes hasta la actualidad incluyen la prueba de la tuberculina como prueba de cribado de la infección tuberculosa, con referencia a las nuevas pruebas diagnósticas basadas en la detección in vitro de interferón-gamma (IGRA) para determinados casos. El objetivo de la presente guía ha sido consensuar y establecer unos criterios comunes para incluir las pruebas IGRA, como una ayuda complementaria a la prueba de la tuberculina en el personal sanitario, a partir de la evidencia disponible en la actualidad. Las recomendaciones de su utilización se han adaptado a las diferentes situaciones en que se pueden encontrar los profesionales que participan en la vigilancia de la salud de los trabajadores sanitarios." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Casas I, Dominguez J, Rodríguez S, Matllo J, Altet N. Guía para la prevención y control de la tuberculosis en el personal sanitario. Med Clin (Barc). 2015;145:534.e1–534.e13." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:2 [ 0 => array:4 [ "etiqueta" => "Annex I" "titulo" => "TST performance and interpretation procedure" "identificador" => "sec0175" "apendiceSeccion" => array:5 [ 0 => array:3 [ "apendice" => "It consists of tuberculin 0.1cc intradermal injection in the ventral aspect of the forearm, preferably in the left arm. I is used tuberculin PPD 2 UT, RT 23 or bioequivalent variety and a diluent with Tween 80. It should be used an insulin type syringe and short bevel needle, 26–27 gauge. If administration is correct, a papule emerges at the injection site, which disappears in a few minutes." "titulo" => "Mantoux technique" "identificador" => "sec0180" ] 1 => array:3 [ "apendice" => "The reading date should be the third day after administration, but readings from the second to the fifth day can also be considered as valid." "titulo" => "Reading date" "identificador" => "sec0185" ] 2 => array:3 [ "apendice" => "The margins of induration should be palpated with the index finger, and good light is required. Maximum margins of induration parallel to the longitudinal axis of the forearm are to be marked and induration be measured crosswise. The presence of erythema alone, without induration, has no value. Induration should be measured in mm, avoiding rounding." "titulo" => "Reading methodology" "identificador" => "sec0190" ] 3 => array:3 [ "apendice" => "No contraindications have been reported. As adverse effects, it rarely causes fever and malaise. In the case of causing blisters, these blisters should be treated as a second-degree burn, once completed the test reading. It can be administered to pregnant women." "titulo" => "Contraindications and adverse effects" "identificador" => "sec0195" ] 4 => array:3 [ "apendice" => "Once open, the Tuberculin containers can be used until empty, regardless of the time elapsed since they began to be used, provided that expiration date is not exceeded. Tuberculin must always be stored in the fridge, approximately at 4°C. Exposure to natural light and fluorescent light should be avoided. The maximum interval between the filling of the syringe and administration is 30min." "titulo" => "Conservation and management of tuberculin" "identificador" => "sec0200" ] ] ] 1 => array:4 [ "etiqueta" => "Annex II" "titulo" => "IGRA performance and interpretation procedure" "identificador" => "sec0205" "apendiceSeccion" => array:5 [ 0 => array:3 [ "apendice" => "The technology involves in vitro stimulation of T cells with mycobacterial antigens, followed by detection of IFN-γ produced by immunological laboratory techniques. The antigens used for stimulation of T cells are specific antigens of M. tuberculosis (ESAT-6, CFP-10 and TB7.7), but absent in BCG vaccine and most environmental mycobacteria. Thus, the sensitized T cells in infected individuals, will release detectable amounts of IFN-γ after being stimulated by the specific antigens of the M. tuberculosis complex." "titulo" => "Theoretical basis of technology" "identificador" => "sec0210" ] 1 => array:3 [ "titulo" => "QuantiFERON®-Gold-In tube method" "identificador" => "sec0215" "apendiceSeccion" => array:3 [ 0 => array:3 [ "apendice" => "For conducting both techniques a blood extraction is necessary. QuantiFERON® method requires collecting blood 3ml, 1ml inoculated in each of the 3 specific tubes for QuantiFERON®. One of them contains specific antigens of M. tuberculosis complex, and the other 2 are the control tubes, one of which is the positive control and one negative control. The tubes can be sent to the laboratory at room temperature, or at 35°C (the antigens are present inside the tube, therefore, stimulation is already occurring). Another possibility is to incubate the tubes at 35°C, until the next day, in the place of blood collection and send them to the lab next day. If shipment does not take place the next day, centrifuge tubes, and preserve the supernatant chilled or frozen. During shipment to the laboratory, temperature must be the same as the sample conservation temperature." "titulo" => "Sample collection and transportation to the laboratory" "identificador" => "sec0220" ] 1 => array:3 [ "apendice" => "QuantiFERON®stimulates T cells present in whole blood and determines the amount of IFN-γ produced through ELISA. In QuantiFERON®the 3 specific antigens of M. tuberculosis (ESAT-6, CFP-10 y TB7.7) are used jointly by stimulation of whole blood." "titulo" => "Basis of the technique" "identificador" => "sec0225" ] 2 => array:3 [ "apendice" => "<a class="elsevierStyleCrossRef" href="#tbl0015">Table 1, Annex II</a>, show the interpreting criteria for QFN-GIT®.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>" "titulo" => "Interpreting the results" "identificador" => "sec0230" ] ] ] 2 => array:3 [ "titulo" => "T-SPOT.TB Technique®" "identificador" => "sec0235" "apendiceSeccion" => array:3 [ 0 => array:3 [ "apendice" => "For T-SPOT-TB® it is necessary to collect blood 8–10ml in CPT tube (containing citrate as anticoagulant) or lithium heparin tube (but without separating gel). The tubes can be immediately sent to the laboratory at room temperature. Alternatively, tubes can be incubated at room temperature until next day in darkness, in the location of blood collection and subsequently be sent to a laboratory at room temperature and protected from light. Once in the laboratory, reagents necessary to stabilize the cells after such a long time from collection might be added to optimize the results." "titulo" => "Sample collection and transportation to the laboratory" "identificador" => "sec0240" ] 1 => array:3 [ "apendice" => "T-SPOT.TB® requires previous separation of peripheral blood mononuclear cells (PBMC) for stimulation and determines the amount of T cells producing IFN-γ through ELISPOT. In T-SPOT.TB® ESAT-6 and CFP-10 antigens are used separately to stimulate PBMC." "titulo" => "Basis of the technique" "identificador" => "sec0245" ] 2 => array:3 [ "apendice" => "<a class="elsevierStyleCrossRef" href="#tbl0020">Table 2, Annex II</a>, show the results. The presence of reactive T cells is observed by the emergence of spots in the bottom of the well of ELISPOT. These spots are counted manually and/or with the help of an automatic reader.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia> <a class="elsevierStyleCrossRef" href="#tbl0025">Table 3, Annex II</a> show the characteristics of both in vitro techniques of diagnosis of tuberculosis infection<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>" "titulo" => "Interpreting the results" "identificador" => "sec0250" ] ] ] 3 => array:3 [ "apendice" => "The use of IGRA in serial screening of health workers shows a large intra-individual variation, with high rates of conversions and reversals. This happens because the optimal interpretation thresholds for test conversion and reversal are not well defined yet. To prevent false conversions and reversals in the serial study, it has been defined an area of uncertainty where the result must be considered limit and the test requires to be repeated to verify the result.<a class="elsevierStyleCrossRefs" href="#bib0350">23,27</a> On the other hand, IGRA can offer indeterminate results. One possibility of indeterminate result is when the negative control obtains an abnormally high result, which invalidates those obtained by the antigens and the positive control. Another indeterminate result occurs when the negative control is correct, the antigen control is negative, but the positive control is also negative. This result also invalidates the test, but it can also be an indicator of lack of response of T cells of the individual, and may indicate anergy and potential immunosuppression. In both cases of indeterminate result, repeating the determination from a new sample is recommended." "titulo" => "Limit results and indeterminate results" "identificador" => "sec0255" ] 4 => array:3 [ "apendice" => "Although not yet fully understood, it seems that the TST can also act as a stimulator of the immune response and, therefore, influence the results of IGRA, the so-called summation reaction or booster effect which is very little likely in the negative, but it is possible in the positive results. To prevent this effect it is recommended that the blood is not extracted for IGRA after the third day since the tuberculin test." "titulo" => "When performing the techniques?" "identificador" => "sec0260" ] ] ] ] ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2392 "Ancho" => 2508 "Tamanyo" => 319943 ] ] "descripcion" => array:1 [ "en" => "Performance in screening if health workers have a previous negative tuberculin skin test. IGRA: in vitro interferon-gamma release assays; TST: tuberculin test; Rx: X-ray; TB: tuberculosis; LTBI: treatment for latent TB infection. * <35 years; recent conversion; immunosuppression; other risk factors." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2392 "Ancho" => 2563 "Tamanyo" => 272330 ] ] "descripcion" => array:1 [ "en" => "Performance in screening if the healthcare providers do not have a previous tuberculin test or the result is unknown. IGRA: in vitro interferon-gamma release assays; TST: tuberculin test; Rx: X-ray; TB: tuberculosis; LTBI: treatment for latent TB infection. * <35 years; recent conversion; immunosuppression; other risk factors." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1761 "Ancho" => 2505 "Tamanyo" => 160505 ] ] "descripcion" => array:1 [ "en" => "Performance against occupational exposure to a case of active tuberculosis if the previous tuberculin test is negative or unknown. IGRA: in vitro interferon-gamma release assays; TST: Tuberculin test; Rx: X-ray; TB: tuberculosis; LTBI: treatment for latent TB infection. * <35 years; recent conversion; immunosuppression; other risk factors." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1380 "Ancho" => 2524 "Tamanyo" => 127679 ] ] "descripcion" => array:1 [ "en" => "Performance against occupational exposure to a case of active tuberculosis if the previous tuberculin test is positive. IGRA: in vitro interferon-gamma release assays; TST: Tuberculin test; Rx: X-ray; TB: tuberculosis; LTBI: treatment for latent TB infection. * <35 years; recent conversion; immunosuppression; other risk factors." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2635 "Ancho" => 2654 "Tamanyo" => 331107 ] ] "descripcion" => array:1 [ "en" => "Performance on contact study jointly considering the results of the TST and IGRA. IGRA: in vitro interferon-gamma release assays; TST: Tuberculin test; Rx: X-ray; TB: tuberculosis; LTBI: treatment for latent TB infection; TPTI: treatment of probable tuberulosis infection." ] ] 5 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Adapted from Jasmer et al.<a class="elsevierStyleCrossRef" href="#bib0325">18</a>" "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Groups of risk \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">Areas of increased risk of exposure to TB cases \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk factors for tuberculosis infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Immigrants from countries with a high prevalence of tuberculosis • Working staff of certain centers or health facilities such as homeless shelters and prisons • Voluntary workers, military medical personnel, taking long trips • Healthcare providers assisting tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High-risk areas are microbiology laboratories, units of infectious diseases, the rooms for bronchoscopy or sputum inductions, emergency rooms, necropsy rooms and those areas where TB patients are treated In areas of high risk of acquiring TB, surveillance should be performed every 6–12 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk factors for developing tuberculosis in an infected person \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Individuals infected or recently reinfected (less than 2 years) • People with modifications in chest X-ray showing an old untreated tuberculosis • Individuals HIV coinfected • People with the following comorbidities: diabetes mellitus, silicosis, leukemia, Hodgkin's disease and other lymphomas, head and neck cancer, lung cancer, chronic renal failure, gastrectomy, intestinal bypass • Transplated • Smokers • People with low weight (10% or over below the ideal weight) • People who abuse alcohol and/or drugs • Individuals immunosuppressed for prolonged therapy with corticosteroids, chemotherapy or anti-TNF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042194.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for tuberculosis infection and development." ] ] 6 => array:9 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Adapted from Rodríguez et al.<a class="elsevierStyleCrossRef" href="#bib0295">12</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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Administration of aerosolized medication \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Techniques of sputum and cough induction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aspiration of respiratory secretions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endotracheal intubation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bronchoscopies and endoscopies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Otolaryngological and maxillofacial examinations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Debridement and cures of tuberculous abscesses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mycobacterial sample handling \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Necropsies \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042195.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Tasks or techniques that increase the risk of exposure to tuberculosis." ] ] 7 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 1, Annex II" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table 1, Annex I" "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="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IFN-γ levels (international units per ml [IU/ml])</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Antigens of Mycobacterium tuberculosis \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">Negative control (Nil) \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">Positive control \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥0.35IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≤8IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.35IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≤8IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥0.5IU/ml \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Range \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.35–0.7IU/lml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≤8IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.35IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≤8IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.5IU/ml \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>8IU/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042192.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Interpretation criteria for QFN-GIT®." ] ] 8 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 2, Annex II" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table 2, Annex I" "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 " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Result: spots count</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Antigens of Mycobacterium tuberculosis</th><th class="td" title="table-head " align="left" valign="top" scope="col">Negative control (Nil) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Positive control \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">ESAT-6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">CFP-10 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " 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">≥6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">and/or \t\t\t\t\t\t\n \t\t\t\t</td><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">≤10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " 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">≤5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">and/or \t\t\t\t\t\t\n \t\t\t\t</td><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">≤10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Range \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">If for either or both antigens it ranges 6–9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">≥20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">and \t\t\t\t\t\t\n \t\t\t\t</td><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">≤10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">and \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042193.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Interpretation criteria for T-SPOT.TB®." ] ] 9 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 3, Annex II" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table 3, Annex I" "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">Variable \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">T-SPOT.TB \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">QuantiFERON® \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sample required \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Blood 8ml (CPT or lithium heparin tubes for PBMC isolation) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Blood 3ml (especial QuantiFERON® tubes) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transportation of blood \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Room temperature with protection from light \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Room temperature or at 35°C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood conservation if the shipment is delayed to the next day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Room temperature with protection from light \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Room temperature or at 35°C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood conservation if the shipment is delayed more days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Separation of PBMCs and refrigerate/freeze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Centrifuging blood, and cooling/freezing supernatants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antigens \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ESAT-6 and CFP-10, separately \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ESAT-6, CFP-10 andTB7.7, simultaneously \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Technical complexity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate-High \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate-Low \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Method of reading \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISPOT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ELISA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reading units \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Number of cells secreting IFN-γ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amount of IFN-γ released \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Types of results \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive, negative, limit or indeterminate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive, negative, limit or indeterminate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Response time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18–24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18–24h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reaction with BCG or MNT \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">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Internal anergy control \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">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042196.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the 2 in vitro techniques of diagnosis of tuberculosis infection." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:47 [ 0 => array:3 [ "identificador" => "bib0240" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global tuberculosis control 2012" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "WHO" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2012" "editorial" => "WHO" "editorialLocalizacion" => "Geneva" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0245" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. 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Prevention and Occupational Health Department of Deloitte (Associació Catalana de Medicina del Treball) (Barcelona). Luis Anibarro. Tuberculosis Unit of the Pontevedra Hospital Complex, Internal Medicine. GEIM (Study Group of mycobacterial infections of the SEIMC [Spanish Society of Infectious Diseases and Clinical Microbiology]) (Pontevedra). Vicente Arias. Occupational Health Department, Hospital General Universitario Gregorio Marañón (Spanish Association of Specialists in Occupational Health) (Madrid). Vicente Ausina. Microbiology Department of the Hospital Universitari Germans Trias i Pujol (Badalona). Irene Barrabeig. Agència de Salut Pública de Catalunya. Epidemiological Surveillance Unit Regió Sanitària Barcelona-Zona Sud. Generalitat de Catalunya (Barcelona). Teresa del Campo. Occupational Health Department and Prevention Department, Fundación Jiménez Díaz, Madrid. (Spanish Association of Specialists in Occupational Health). Madrid. Joan A. Caylà. Epidemiology Department. 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Medicine laboratory, Hospital Universitario Central de Asturias, GEIM (Study Group of mycobacterial infections of the SEIMC [Spanish Society of Infectious Diseases and Clinical Microbiology]) (Oviedo). Anna Rodés. Agència de Salut Pública de Catalunya. Public Health Surveillance Unit. Generalitat de Catalunya (Barcelona). Juan Ruiz-Manzano. Microbiology Department of the Hospital Universitari Germans Trias i Pujol. Member of TIR Area and PII of Tuberculosis. (SEPAR) (Badalona). Pilar Solans. Territorial management of Primary Care Barcelona Ciutat de l’ICS (Barcelona)." 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Consensus statement

Guidelines for the prevention and control of tuberculosis in health care workers

Guía para la prevención y control de la tuberculosis en el personal sanitario

Irma Casasa,b, Jose Dominguezb,c,d,

Corresponding author

jadomb@gmail.com

Corresponding author.

, Soledad Rodrígueze, Joan Matllof, Neus Altetg

a Servicio de Medicina Preventiva, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

b Universitat Autònoma de Barcelona, Barcelona, Spain

c Servicio de Microbiología, Institut d’Investigació Germans Trias i Pujol, Badalona, Barcelona, Spain

d CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain

e Servicio de Prevención de Riesgos Laborales, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat , Barcelona, Spain

f Servicio de Prevención de Riesgos Laborales, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

g Unitat de Prevenció i Control de la Tuberculosi de Barcelona, Barcelona, Spain

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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Performance on contact study jointly considering the results of the TST and IGRA&#46; IGRA&#58; <span class="elsevierStyleItalic">in vitro</span> interferon-gamma release assays&#59; TST&#58; Tuberculin test&#59; Rx&#58; X-ray&#59; TB&#58; tuberculosis&#59; LTBI&#58; treatment for latent TB infection&#59; TPTI&#58; treatment of probable tuberulosis infection&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction and methodology</span><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberculosis &#40;TB&#41; remains today one of the infectious diseases with highest global morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">1&#44;2</span></a> The species grouped in <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> &#40;<span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#41; complex are the causative agents of TB&#46; The main reservoir is infected human being and the source of infection the sick person&#44; especially a person with cough&#44; pulmonary cavitary lesion and acid-alcohol resistant bacilli &#40;AARB&#41; in sputum&#46; The most important route of transmission is air&#44; by contaminated aerosols coming from the breath of sick people&#44; which have the ability to remain suspended in the ambient air&#46; We should also consider the transmission in laboratories handling contaminated biological samples&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The most common form of the disease is in the lung&#44; whereas 20&#8211;40&#37; of cases have an extrapulmonary or mixed location &#40;miliary&#44; lymph nodes&#44; genitourinary&#44; osteoarticular&#44; or meningeal&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In Europe&#44; TB remains a major public health problem&#46; In 2010&#44; 388&#44;875 cases of TB were reported in 52 countries in Europe &#40;incidence rate of 43&#46;2 per 100&#44;000 population&#41;&#44; with significant variability among different countries&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">4</span></a> This region contains about 4&#46;7&#37; of all cases detected worldwide&#46; Notification of the countries of the European Union and the European Economic Area follows a downward trend with a 4&#37; average rate&#46; Spain&#44; with a rate of 13&#46;04 cases per 100&#44;000 population in 2012&#44; continues to have gross rates above the average of the countries of the European Union and the European Economic Area with a significant variability among the autonomous communities&#44; ranging from 6&#46;5 cases per 100&#44;000 in the Canary Islands&#44; to 24&#46;6 cases per 10<span class="elsevierStyleSup">5</span> in Galicia&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In this scenario&#44; healthcare providers &#40;HCP&#41; working in a center where patients are treated for TB may be exposed to this occupational hazard&#46; Healthcare providers have reported in our environment high incidence of tuberculosis infection &#40;15&#46;4&#37; at 4 years of follow-up&#41; although there has been a downward trend in recent years&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">6</span></a> A systematic review in middle and low income countries estimated annual risk of tuberculosis infection ranging from 3&#46;9 to 14&#46;3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">7</span></a> Similarly&#44; the incidence of tuberculosis in healthcare providers has been declining in recent years&#44; but there is still high occupational risk of TB in these professionals&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">8&#8211;10</span></a> In another systematic review it was estimated that the annual risk of developing TB was 3 times higher in the healthcare providers compared to the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">8</span></a> This risk is not the same in all working areas or units&#44; being highest in emergency rooms&#44; microbiology and pathology laboratories&#44; as well as in units where certain procedures such as sputum induction or bronchoscopies are performed&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In order to reduce this risk it is important to be provided with measures of infection control in healthcare providers&#46; One of the most important measures is the training of health personnel in the early diagnosis of patients with TB&#44; as well as respiratory isolation measures and the use of respirators&#46; Another important measure is to monitor health personnel regularly by screening techniques for tuberculosis infection&#46; The health personnel screening should be performed for 2 main reasons&#46; One purpose is to prevent the transmission from healthcare providers to patients by detecting early TB cases in health personnel&#46; A second purpose is to detect and treat early TB infection in healthcare providers in order to prevent the development of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The existing national guidelines currently include the tuberculin skin test &#40;TST&#41; as a screening test for TB infection&#44; referring to interferon gamma release assays &#40;IGRA&#41; for a number of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">12&#8211;14</span></a> This guideline was an initiative of the Institut Catal&#224; de la Salut based on evidence available today&#46; Its purpose has been to reach a consensus and establish common criteria to include IGRA assays as an additional aid to the TST in healthcare providers&#46; The recommendations of use have been adapted to different situations&#58; screening of infection in healthcare providers&#44; both at the time of incorporation at work and periodically&#46; Performance when tuberculosis is suspected in healthcare providers&#59; and performance against accidental exposure to a patient with TB or material potentially infected&#46; Subsequently&#44; the invitation was extended to involve various medical and scientific societies of our country&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In short&#44; this guideline aims to be a tool that allows the professionals involved in monitoring the health of health professionals to address&#44; efficiently&#44; the study not only of tuberculosis&#44; but also of tuberculous infection in healthcare&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This guidelines has been divided into several sections&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Diagnosis of infection and&#47;or tuberculosis disease</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Screening for tuberculosis infection in healthcare providers</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Performance against accidental exposure to a patient with active TB</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Performance of Prevention Department against cases of TB or suspected TB in healthcare providers</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Occupational aptitude criteria</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall">General preventive measures</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Preventive measures in healthcare providers specially susceptible</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Preventive measures in pregnancy and lactation</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">This guideline is supported by the following companies and scientific organizations&#58; Spanish Society of Pneumology and Thoracic Surgery &#40;SEPAR&#41;&#44; Study Group on mycobacterial infections &#40;GEIM&#41; of the Spanish Society of Infectious Diseases and Clinical Microbiology &#40;SEIMC&#41;&#44; Spanish Association of Specialists in Occupational Medicine &#40;AEEMT&#41; and Program on prevention and control of TB of the Public Health Agency of Catalonia&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Diagnosis of infection and&#47;or tuberculosis disease</span><p id="par0090" class="elsevierStylePara elsevierViewall">The information in order to establish the diagnosis of infection and&#47;or tuberculosis should be obtained through&#58;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Occupational hazard assessment</span><p id="par0095" class="elsevierStylePara elsevierViewall">It will take place in every workplace and will be performed by the risk prevention technical staff<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">11&#44;15&#44;16</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; risk areas&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Anamnesis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Specific anamnesis is required to investigate personal and family history of tuberculosis&#44; previous TST and&#47;or IGRA with investigation&#44; if necessary&#44; of the state of infection&#44; previous treatment with anti-TB drugs and previous BCG vaccination&#46; It is considered that a person has been vaccinated with BCG if they have the typical scar and&#47;or provide the vaccination card proving it&#46; It should also be aimed at identifying risk groups both in TB infection and progression to TB disease<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">14&#44;17&#44;18</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Specific clinical examination</span><p id="par0105" class="elsevierStylePara elsevierViewall">It should be aimed at detecting clinical features that can increase the probability of TB acquisition and&#47;or transmission&#44; and detecting the symptoms and signs of this disease&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Additional examinations</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Tuberculin skin test<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">19</span></a></span><p id="par0110" class="elsevierStylePara elsevierViewall">All healthcare providers should undergo this test when recruited&#44; and serially&#44; to those at risk for TB infection&#44; except for those providing documentation proving previous positive results consistent with TB infection or who have suffered TB&#46; The procedure of performing and reading the TST is specified in <a class="elsevierStyleCrossRef" href="#sec0175">Annex I</a>&#46; Because of the difficulty to interpret the results&#44; booster effect is not recommended&#46; Thus&#44; a technical IGRA is required to prevent it&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Interferon-gamma <span class="elsevierStyleItalic">in vitro</span> assays</span><p id="par0115" class="elsevierStylePara elsevierViewall">They are based on the interferon-gamma detection &#40;IFN-&#947;&#41; released in response to <span class="elsevierStyleItalic">in vitro</span> stimulation of sensitized T cells present in peripheral blood with <span class="elsevierStyleItalic">M&#46; tuberculosis</span> specific antigens&#46; The amount of IFN-&#947; produced can be measured <span class="elsevierStyleItalic">&#40;QuantiFERON</span><span class="elsevierStyleSup">&#174;</span><span class="elsevierStyleItalic">-Gold-In tube&#59; QIAGEN&#44; D&#252;sseldorf&#44; Germany&#41;</span> as well as the number of mononuclear cells producing it through specific stimulation <span class="elsevierStyleItalic">&#40;T-SPOT&#46;TB</span><span class="elsevierStyleSup">&#174;</span><span class="elsevierStyleItalic">&#59; Oxford Immunotec&#44; Oxford&#44; United Kingdom&#41;</span>&#46; <span class="elsevierStyleItalic">QuantiFERON</span><span class="elsevierStyleSup">&#174;</span><span class="elsevierStyleItalic">-Gold-In tube</span> uses specific antigens of <span class="elsevierStyleItalic">M&#46; tuberculosis</span> &#40;ESAT-6&#44; CFP-10 y TB7&#46;7&#41;&#44; but T-SPOT&#46;TB<span class="elsevierStyleSup">&#174;</span>&#44; stimulated with ESAT-6 y CFP-10&#44; is generally considered to be more sensitive since it obtains more positive results&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">20&#44;21</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Chest X-ray</span><p id="par0120" class="elsevierStylePara elsevierViewall">If TST and&#47;or IGRA are positive&#44; tuberculosis should be excluded through a radiological study&#46; It should also be performed in the healthcare providers with a negative TST or IGRA&#44; but with comorbidities causing immunosuppression&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Other tests</span><p id="par0125" class="elsevierStylePara elsevierViewall">If tuberculosis is suspected&#44; always according to the strict indication of the medical staff&#44; bacteriological analysis and other diagnostic tests can be performed until obtaining disease confirmation or exclusion&#46;</p></span></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Screening for tuberculosis infection in healthcare providers</span><p id="par0130" class="elsevierStylePara elsevierViewall">The TST and&#47;or IGRA&#44; as baseline screening&#44; are recommended in subjects working in the healthcare system&#44; regardless of the risk associated with their job&#46; In general&#44; neither TST nor the IGRA are to be used to investigate periodically people at low risk of tuberculosis infection or disease&#46; Therefore&#44; it is important to classify the healthcare providers according to the occupational risk of infection and their personal risk of disease if infected&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Healthcare providers are considered to have a positive TST if induration is not below 5<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">14</span></a> It should be noted that BCG does not prevent TB infection and&#44; therefore&#44; the TSTs ranging 5&#8211;14<span class="elsevierStyleHsp" style=""></span>mm may be due to either tuberculous infection or BCG vaccination or nontuberculous mycobacteria&#46; The more time has elapsed since vaccination &#40;15 years or more&#41; and the larger the diameter of the TST induration&#44; the higher the probability that the reaction is due to TB infection&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">22</span></a> In studies of high-risk-infection contacts and workers &#40;HIV infected&#44; immunosuppressive therapy or symptoms suggesting TB&#41;&#44; history of vaccination must not be taken into account and TST will be considered positive if it is equal or above 5<span class="elsevierStyleHsp" style=""></span>mm&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a> shows the interpreting criteria of T-SPOT&#46;TB and QuantiFERON<span class="elsevierStyleSup">&#174;</span>-Gold-In tube&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">23</span></a> If IGRA are &#8220;indeterminate&#8221; they should be repeated to confirm the result&#44; and evaluate the possibility of a potential technical error or immunosuppression&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">IGRA have shown a good correlation with risk factors of exposure to TB in places of low incidence of the disease&#46; But their use in serial screening of healthcare providers show significant intraindividual variation&#44; with high conversion and reversal rates&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">24&#8211;26</span></a> This is because the optimal performance thresholds for test conversion and reversal have not been well defined yet&#46; To prevent false conversions and reversals in the serial study&#44; it has been defined an area of uncertainty where the result must be considered limit &#40;<a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a>&#41; and the test requires to be repeated to verify the result&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">23&#44;27</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The use of IGRA instead of the TST as the sole screening test produces a lower prevalence of positive tests and&#44; therefore&#44; the number of health workers who receive unnecessary treatment for TB infection will decrease&#46; It also has important advantages over the TST&#44; such as preventing the booster effect as well as logistic advantages for being an <span class="elsevierStyleItalic">in vitro</span> test&#58; confidentiality&#44; it is not necessary a second visit&#44; and its interpretation is more objective than TST&#46; Consequently&#44; in the case of health workers with a negative TST&#44; serial screening test can still be performed with the TST&#46; If tuberculin conversion is detected&#44; IGRA is recommended&#46; To decide the therapeutic action it is necessary to evaluate important factors&#44; such as&#58; contact with TB case&#44; personal risk factors&#44; BCG vaccination&#44; history of previous TST and date&#44; induration intensity and other diagnostic information&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Regular monitoring&#44; once the healthcare providers already have a positive TST but negative IGRA&#44; should be performed through IGRA&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In centers where IGRA is not available&#44; monitoring will continue to be performed with the TST&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The recommendations of joint use of TST and IGRA are presented according to the initial results of the TST&#44; as follows&#58;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">If healthcare providers already have a previous positive tuberculin test</span><p id="par0170" class="elsevierStylePara elsevierViewall">IGRA determination is recommended to have a baseline result&#46; This information may be important to assess the performance against a potential occupational exposure of these workers to TB patients&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">If healthcare providers already have a previous negative tuberculin test</span><p id="par0175" class="elsevierStylePara elsevierViewall">In the case of health workers with a previous negative TST&#44; they should undergo another TST and proceed in accordance with <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">If healthcare providers do not have a previous tuberculin test or the result is unknown</span><p id="par0180" class="elsevierStylePara elsevierViewall">If healthcare providers do not have a previous tuberculin test or the result is unknown&#44; a new TST is required and it should be proceeded in accordance with <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">All staff with a positive result of TST and&#47;or IGRA should undergo a simple chest X-ray and anamnesis in order to dismiss active TB disease&#46; If dismissed&#44; it is considered that the person has TB infection&#46; For the purposes of subsequent risk of developing TB disease and its management&#44; the following different situations should be considered&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recent TB infection or tuberculin conversion</span>&#58; when the worker&#39;s TST and&#47;or IGRA has been positivized in less than 2 years&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Tuberculous infection without conversion criteria&#58;</span> a worker shall be deemed to have tuberculous infection without conversion criteria when the TST and&#47;or IGRA has been positivized in over two years&#46;</p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Frequency of monitoring</span><p id="par0200" class="elsevierStylePara elsevierViewall">Exposure to TB patients is an occupational risk factor for healthcare professionals&#46; All personnel newly recruited should undergo specific monitoring&#44; compulsorily&#46; Regular monitoring of health workers who have negative results at baseline screening is necessary in order to detect their risk to exposure&#46; This requirement is based on the classification of the risk of TB transmission in the workplace and the risk of healthcare workers of developing the disease if infected with the TB bacillus&#46; Periodically it should be assessed whether a given workplace has the same transmission risk or it has changed&#44; and if the medical staff has the same risk of disease&#44; if infected&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Groups with no high risk of TB infection or disease need not be screened routinely to optimize resources&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Performance against accidental exposure to a patient with active tuberculosis</span><p id="par0210" class="elsevierStylePara elsevierViewall">If an accidental occupational exposure to a patient with active TB occurs&#44; we should proceed to monitor the state of all staff in contact with the case&#46; Accidental exposure is the contact with a TB patient not having taken the right measures of air isolation&#46; The main cause of accidental exposure is the delayed diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">28&#44;29</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The criteria for deciding whether or not a worker should be tested&#44; will be applied based on the time of contact with the source and degree of infectiousness of the patient&#44; as well as the degree of immunosuppression of the exposed person&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">The investigations carried out and measures taken must be recorded in the medical history of the healthcare providers&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The actions to be taken in this research are as follows&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">1&#46;</span><p id="par0230" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Index case &#40;IC&#41; data collection&#58;</span> the person infected with TB has to be evaluated &#40;clinical symptoms and delayed diagnosis&#44; type of injury&#44; microbiological study of sputum&#41;&#44; which is related to the ability of the patient to aerosolize bacilli and the number of bacilli that are aerosolized&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">30&#44;31</span></a> Practically&#44; any patient in which the <span class="elsevierStyleItalic">M&#46; tuberculosis</span> has been isolated from a respiratory sample other than that of a biopsy can be described as potential TB bacillus transmitter&#46; The smear-positive patient is the major transmitter of the disease&#46; The higher levels of bacilli&#44; the more infectiousness&#46; If the smear is negative but culture is positive&#44; even though the patient can transmit the disease&#44; the degree of infectiousness is lower&#46; Patients with cough and cavitation on chest X-ray are the most infectious&#46; In addition&#44; the more days have elapsed until air isolation measures have been established for the patient&#44; the higher risk of transmission&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">2&#46;</span><p id="par0235" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Registration of personnel exposed&#58;</span> The person in charge is the assisting person&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">3&#46;</span><p id="par0240" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Personnel exposed&#58;</span> assessment of the degree of exposure to the case &#40;time of exposure&#44; frequency and risk tasks or techniques&#41;&#46; The risk tasks or techniques are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">12</span></a> Concentric circles&#44; being HCP investigation a priority with a cumulative exposure of 8<span class="elsevierStyleHsp" style=""></span>h if the case is bacilliferous&#44; or 40<span class="elsevierStyleHsp" style=""></span>h if the smear is negative but the sputum culture is positive&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">32</span></a> The immunosuppressed HCP and HCP with sporadic contact but having performed risk tasks or techniques to the case without the proper respiratory protection measures will also be deemed as a priority&#46; The diagnostic evaluation and therapeutic approach are determined in <a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">4&#46;</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Notification of accidental exposures such as work accidents without a sick leave&#58;</span> to the Mutua de Accidentes de Trabajo y Enfermedades Profesionales &#40;Mutual of Accidents and Occupational Diseases&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">5&#46;</span><p id="par0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Verify</span> compliance with the protocols to prevent future accidental exposures&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">29</span></a></p></li></ul></p><p id="par0255" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a> show the algorithm against occupational exposure to active TB cases according to the result of the TST and IGRA&#46; In this case&#44; TST is considered positive when induration &#8805;5<span class="elsevierStyleHsp" style=""></span>mm and &#8805;6<span class="elsevierStyleHsp" style=""></span>mm increase if baseline TST was negative&#46; IGRAs are considered positive or negative as described in <a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a>&#46; In the study of accidental exposure&#44; limit results should be considered as positive&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Performance of the Prevention Department against cases of TB or suspected TB in healthcare providers</span><p id="par0260" class="elsevierStylePara elsevierViewall">If it is detected that the worker has a clinical symptomatology consistent with TB disease or TB already confirmed&#44; 2 types of investigation should be initiated&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">a&#41;</span><p id="par0265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conventional investigation of contacts&#58;</span> aimed at contacts of healthcare providers in order to investigate whether or not there transmission of infection has occurred&#46; The study of occupational contacts will be the responsibility of the Prevention Department&#46; Non-occupational contacts &#40;family&#44; community and patients&#41; will be the responsibility of the Units of Epidemiological Surveillance and welfare centers&#46; Patients in contact with the medical staff should be checked up to find the possible source of infection &#40;although non-occupational transmission cannot be ruled out&#41; or possible cases of transmission&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">33</span></a></p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">b&#41;</span><p id="par0270" class="elsevierStylePara elsevierViewall">It should also be reviewed whether or not the protocols to prevent transmission of tuberculosis infection have been correctly completed&#46;</p></li></ul></p><p id="par0275" class="elsevierStylePara elsevierViewall">The infectivity of healthcare providers infected with TB should be evaluated &#40;clinical symptoms and delayed diagnosis&#44; type of injury&#44; microbiological study of sputum&#41;&#44; which is related to the ability of the patient to aerosolize the bacilli and the number of bacilli that are aerosolized&#46; Practically&#44; any person to whom <span class="elsevierStyleItalic">M&#46; tuberculosis</span> has been isolated from a respiratory specimen other than from a biopsy can be defined as a potential transmitter of tubercle bacilli&#46;</p><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Period of infectiousness</span><p id="par0280" class="elsevierStylePara elsevierViewall">Delayed diagnosis is a determining factor for the period of infectiousness of a patient&#46; The onset of infectiousness cannot be determined objectively&#46; The onset of cough is usually used as the time when the transmission begins&#59; in the absence of cough&#44; the onset of any respiratory symptoms attributable to TB&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">To determine the period of infectiousness during which contacts have been exposed and which should be investigated within the conventional contact study&#44; the following rules can be used<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">34</span></a>&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">1&#41;</span><p id="par0290" class="elsevierStylePara elsevierViewall">In an AARB patient&#44; the period of infectivity begins 3 months before the collection of the first positive sample of sputum or from the onset of clinical symptoms&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">2&#41;</span><p id="par0295" class="elsevierStylePara elsevierViewall">Patients with 2 negative sputum samples &#40;without AARB&#41;&#44; but with positive culture can be deemed potentially infectious for a period of one month before the date of TB diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">3&#41;</span><p id="par0300" class="elsevierStylePara elsevierViewall">Coughing or having cavitated lesions increases the degree of infectiousness&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">4&#41;</span><p id="par0305" class="elsevierStylePara elsevierViewall">The period of infectiousness of the disease sets the limits on contact investigation&#46; By definition&#44; in relation to the study of contacts&#44; this period ends&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">a&#41;</span><p id="par0310" class="elsevierStylePara elsevierViewall">At the time the relationship between the IC and the contact is ended&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">b&#41;</span><p id="par0315" class="elsevierStylePara elsevierViewall">When air isolation is established&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">c&#41;</span><p id="par0320" class="elsevierStylePara elsevierViewall">The date the first negative sputum sample is collected&#46;</p></li></ul></p></li></ul></p><p id="par0325" class="elsevierStylePara elsevierViewall">For practical purposes&#44; it is considered that the patient is no longer infectious when has received adequate specific treatment for 15&#8211;21 days&#44; there is clinical improvement and 3 negative sputum samples &#40;without AARB&#41; have been collected every other day&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">11&#44;35</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Risk of exposure and contact study prioritization</span><p id="par0330" class="elsevierStylePara elsevierViewall">Conventionally&#44; contacts have been classified within &#8220;concentric circles&#8221; around the IC&#44; taking into account infectiousness&#44; the intensity and duration of exposure to IC and risk of disease of contact person&#44; if infected&#46; In each contact study&#44; it should be specified which of these circles corresponds personnel exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">34</span></a> With the current evidence&#44; the following considerations will be taken into account&#58;</p><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">First circle of contacts</span><p id="par0335" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">a&#41;</span><p id="par0340" class="elsevierStylePara elsevierViewall">Health personnel with 8<span class="elsevierStyleHsp" style=""></span>h cumulative exposure to a bacilliferous IC or cumulative 40<span class="elsevierStyleHsp" style=""></span>h if the smear is negative and the sputum culture is positive&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">b&#41;</span><p id="par0345" class="elsevierStylePara elsevierViewall">Health workers with some type of immunosuppression&#46;</p></li></ul></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Second circle of contacts</span><p id="par0350" class="elsevierStylePara elsevierViewall">Health personnel with less than 8<span class="elsevierStyleHsp" style=""></span>h cumulative exposure to a bacilliferous IC or less than cumulative 40<span class="elsevierStyleHsp" style=""></span>h if the smear is negative and the sputum culture is positive&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Third circle of contacts</span><p id="par0355" class="elsevierStylePara elsevierViewall">Health workers with sporadic contact with the IC&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">Prioritization of the contact study begins with the first circle&#44; followed by the second and then the third circle&#46; But it is very important to consider that the risk of disease by a recent infection is high&#44; as previously discussed&#46; The priority of the contact rises from one circle to next when there are other risk factors&#46; Therefore&#44; the immunosuppressed patients of any etiology always belong to the first circle&#44; even though their degree of contact is in the third circle&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a> shows the evaluation algorithm and therapeutic approach to be followed in the study of the HPC contacts with TB&#44; considering the joint use of the TST and IGRA&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0370" class="elsevierStylePara elsevierViewall">In this case&#44; TST is considered positive when induration &#8805;5<span class="elsevierStyleHsp" style=""></span>mm and &#8805;6<span class="elsevierStyleHsp" style=""></span>mm increase if baseline TST was negative&#46; IGRAs are considered positive or negative according to <a class="elsevierStyleCrossRef" href="#sec0205">Annex II</a>&#46; In the study of contacts&#44; the limit results should be considered as positive&#46; Finally&#44; it should be noted that if the TST was positive previously&#44; patients should undergo IGRA&#46;</p></span></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Occupational aptitude criteria</span><p id="par0375" class="elsevierStylePara elsevierViewall">Any worker with pulmonary or airways TB have to be separated temporarily from their workplace for a minimum period of 2&#8211;3 weeks from the onset of specific treatment&#44; taking into account the periods of infectiousness previously mentioned&#46; The staff member should be reassessed before discharge and reintegration into the workplace&#46;</p><p id="par0380" class="elsevierStylePara elsevierViewall">The infected staff&#44; whether or not following treatment of tuberculosis infection &#40;TTI&#41;&#44; can continue to work&#44; since it does not pose a risk to other people or patients&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">General preventive measures</span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Collective measures</span><p id="par0385" class="elsevierStylePara elsevierViewall">Measures must be applied in all centers treating patients with a diagnosis or suspected diagnosis of active respiratory TB&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">11&#44;36&#44;37</span></a></p><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Administrative measures</span><p id="par0390" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0395" class="elsevierStylePara elsevierViewall">Identification&#44; isolation&#44; diagnosis and early treatment of patients with TB disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0400" class="elsevierStylePara elsevierViewall">Proper air isolation of patients with pulmonary or laryngeal TB<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">35&#44;38</span></a>&#58; the person has to use surgical mask during transfers and while in waiting or common areas&#44; and must follow proper respiratory hygiene&#46; In primary care&#44; if TB is suspected in a person coughing&#44; this person should be provided with a surgical mask&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0405" class="elsevierStylePara elsevierViewall">The staff must have ongoing training regarding the signs and symptoms of TB&#44; transmission mechanisms and prevention&#46;</p></li></ul></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Structural measures</span><p id="par0410" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">&#8226;</span><p id="par0415" class="elsevierStylePara elsevierViewall">Patient&#39;s room&#58; the room must be always individual and it should ideally be provided with a ventilation system with a powerful air extractor and negative pressure&#44; with a renewed air every 6&#8211;12<span class="elsevierStyleHsp" style=""></span>times&#47;h&#46; The air outlet to the outside must always be away from an air inlet or locations where there are other people&#46; The door must always be closed&#44; preferably by means of an automated system&#46; The windows should be open as long as possible&#44; and the room must be provided with an individual bathroom&#46; If the air has to recirculate to other units of the hospital&#44; HEPA filters are required&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">&#8226;</span><p id="par0420" class="elsevierStylePara elsevierViewall">Medical waste&#58; all waste containing respiratory secretions of the patient will be segregated in a bag that should be sealed&#44; before leaving the room&#44; and be treated as specific Group III medical waste&#46;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Mycobacteria laboratories&#58; the facilities must be containment level 3 and separated from other laboratories&#46; Access must be through a double door system&#46; The laboratory must be provided with an airflow regulating system&#46; All the air on its way out of the facilities must pass through the HEPA filters&#46; They also have to be equipped with type 2 or 3 biological safety cabinets for handling infected samples and storing regular personal protective equipment&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">39</span></a></p></li></ul></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Individual measures</span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Individual protection equipment<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">40</span></a></span><p id="par0430" class="elsevierStylePara elsevierViewall">The staff will use high filtration mask&#44; type FFP2&#44; when in contact with a bacilliferous or suspected bacilliferous patient &#40;room&#44; <span class="elsevierStyleItalic">etc&#46;</span>&#41;&#46; The personnel responsible for pentamidine aerosolization&#44; sputum induction&#44; bronchoscopy&#44; necropsy or alike&#44; mycobacteria laboratories&#44; handling urine of patients with TB or TB abscess drainage&#44; must use a FFP3 protective mask&#46; These masks are for personal use and replacement is recommended if they are dirty or damaged&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Treatment of tuberculosis infection</span><p id="par0435" class="elsevierStylePara elsevierViewall">It is aimed at preventing the development of the disease in people who have been infected&#46; Therefore&#44; it is important to exclude the disease before starting the TTI&#46; People at increased risk of developing the disease if infected&#44; are described in the specific section regarding special susceptibility&#46;<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">&#8226;</span><p id="par0440" class="elsevierStylePara elsevierViewall">Indications&#58; treatment is indicated for all staff with a tuberculin conversion&#44; regardless of age&#59; in those with tuberculosis infection without conversion criteria but aged under 35&#59; and workers with residual lesions consistent with TB never treated before&#46; The person should be informed of the risks and benefits of treatment to ensure proper compliance&#46;</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">&#8226;</span><p id="par0445" class="elsevierStylePara elsevierViewall">Treatment schedule&#58; The duration of treatment is 6 months &#40;minimum&#41; to 12 months &#40;optimal&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">19</span></a> The treatment regimen with isoniazid &#40;H&#41; daily for 52 weeks&#44; with over 80&#37; compliance manages to prevent the development of the disease in more than 90&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">41</span></a> But a very significant factor in the effectiveness of TTI is to get the patient to take the necessary doses of medication&#46; Because it is difficult to obtain a proper compliance in long-term regimes&#44; the 6-month regimen of H &#40;6 H&#41; is the most cost-effective schedule&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">42</span></a> H intake should be in a single dose of 300<span class="elsevierStyleHsp" style=""></span>mg&#47;day and fasting&#46; In cases of intolerance or resistance to H it is advisable to use rifampicin &#40;R&#41; for a period of 4 months &#40;4 R&#41;&#46;</p></li></ul></p><p id="par0450" class="elsevierStylePara elsevierViewall">An alternative is to use the H<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>R regimen for 3 months &#40;3 HR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">43</span></a> This regimen&#39;s efficacy &#40;evidence&#41; and toxicity are similar to that of 6 H&#44; and compliance is best&#46; Therefore&#44; it should be deemed as an alternative regimen&#46; It is an easy regimen&#44; because both drugs are associated in marketed formulations&#46;</p><p id="par0455" class="elsevierStylePara elsevierViewall">The use of R<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>pyrazinamide is not recommended for 2 months &#40;2 RZ&#41; due to its toxicity&#44; although in people coinfected with HIV it is best tolerated&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">44</span></a></p><p id="par0460" class="elsevierStylePara elsevierViewall">In the absence of teratogenic effects caused by these drugs&#44; they can be administered during pregnancy and lactation&#46;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">&#8226;</span><p id="par0465" class="elsevierStylePara elsevierViewall">Contraindications&#58; history of adverse reactions to drugs used and decompensated acute or chronic liver disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">&#8226;</span><p id="par0470" class="elsevierStylePara elsevierViewall">Follow-up&#58; Before starting treatment&#44; examination of liver function is recommended&#46; Monitoring is performed basically to dismiss hepatotoxicity and other adverse effects and to enhance compliance with treatment through health education&#46; Additional determination of liver function during the first 3&#8211;6 weeks of treatment is recommended&#46; The treatment of infection should be discontinued if transaminase levels reach 3 times the upper limit of normal levels and patient has symptoms&#46; Also if the level is 5 times over normal levels while the patient is asymptomatic&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">19&#44;45</span></a></p></li></ul></p></span></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Organizational measures</span><p id="par0475" class="elsevierStylePara elsevierViewall">If a recent or suspected TB infection or diagnosis of tuberculosis disease is detected&#44; it will be reported to the technical area in order to review the risk assessment of the workplace and the corrective measures proposed&#46; Notification to the local public health services of the medical center is compulsory&#46;</p><p id="par0480" class="elsevierStylePara elsevierViewall">Pulmonary TB is an individualized disease&#44; and must be reported promptly&#44; as provided by the health authorities&#46;</p><p id="par0485" class="elsevierStylePara elsevierViewall">Due to the emergence of the process in the workplace&#44; it must be notified to the relevant MATEPSS as a professional contingency &#40;occupational accident or disease&#41; through the human resources management&#47;unit of the center or area &#40;RD1299&#47;2006&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">46</span></a></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Preventive measures in special susceptibility workers</span><p id="par0490" class="elsevierStylePara elsevierViewall">Those workers particularly susceptible to the risk of TB should be identified and it should be assessed whether or not their job is a risk to their special susceptibility&#46; Particularly susceptible circumstances are as follows&#58;<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">&#8226;</span><p id="par0495" class="elsevierStylePara elsevierViewall">Immigration from countries with high incidence of TB&#46; The risk of developing the disease is higher within the first 5 years since their arrival&#46;</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">&#8226;</span><p id="par0500" class="elsevierStylePara elsevierViewall">Chronic renal failure&#46;</p></li><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">&#8226;</span><p id="par0505" class="elsevierStylePara elsevierViewall">Immunodeficiencies&#46;</p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">&#8226;</span><p id="par0510" class="elsevierStylePara elsevierViewall">Silicosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">&#8226;</span><p id="par0515" class="elsevierStylePara elsevierViewall">HIV infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">&#8226;</span><p id="par0520" class="elsevierStylePara elsevierViewall">Diabetes <span class="elsevierStyleItalic">mellitus&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">&#8226;</span><p id="par0525" class="elsevierStylePara elsevierViewall">Long-term therapy with corticosteroids&#46;</p></li><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">&#8226;</span><p id="par0530" class="elsevierStylePara elsevierViewall">Transplants&#46;</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">&#8226;</span><p id="par0535" class="elsevierStylePara elsevierViewall">Immunosuppressive therapy &#40;chemotherapy or anti-TNF&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">&#8226;</span><p id="par0540" class="elsevierStylePara elsevierViewall">Chronic inflammatory disease or rheumatic diseases such rheumatoid arthritis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">&#8226;</span><p id="par0545" class="elsevierStylePara elsevierViewall">Leukemias&#44; lymphomas and other neoplastic processes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">&#8226;</span><p id="par0550" class="elsevierStylePara elsevierViewall">Gastrectomy and intestinal bypass&#46;</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">&#8226;</span><p id="par0555" class="elsevierStylePara elsevierViewall">A history of drug dependence&#46;</p></li></ul></p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Preventive measures in pregnancy and lactation</span><p id="par0560" class="elsevierStylePara elsevierViewall">Pregnancy is not considered a situation of special susceptibility&#44; since for most of working females the risk of infection is not higher than in the general population&#46; However&#44; the following should be taken into account<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">12&#44;47</span></a>&#58;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">&#8226;</span><p id="par0565" class="elsevierStylePara elsevierViewall">There is no evidence that the TST has adverse effects on pregnant women or the fetus&#44; but it should only be performed if there are risk factors for infection and progression to TB disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">&#8226;</span><p id="par0570" class="elsevierStylePara elsevierViewall">Pregnancy does not increase the risk of developing the disease&#46; Thus&#44; in the case of diagnosing TB infection&#44; it is recommended that the TTI be postponed&#46; It is advisable to start after 2&#8211;3 weeks postpartum to prevent potential hepatotoxicity of H in the immediate postpartum period&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">&#8226;</span><p id="par0575" class="elsevierStylePara elsevierViewall">TTI is recommended in women at high risk of progression from infection to tuberculosis &#40;recently infected women or women coinfected with HIV&#41;&#46; In these cases the initiation of treatment need not be delayed&#44; even if in the first quarter of pregnancy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">&#8226;</span><p id="par0580" class="elsevierStylePara elsevierViewall">The treatment of choice in the TTI is the 6 H regimen &#40;with pyridoxine supplements&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">&#8226;</span><p id="par0585" class="elsevierStylePara elsevierViewall">Breastfeeding is not contraindicated if the mother is following TTI&#44; because even though drugs are excreted in human milk&#44; they do so in very small concentrations as to produce adverse effects on the infant&#46;</p></li><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">&#8226;</span><p id="par0590" class="elsevierStylePara elsevierViewall">If TB disease has been diagnosed during pregnancy&#44; treatment should not be delayed because untreated TB means higher risk for both pregnant woman and fetus&#46;</p></li></ul></p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Conflict of interests</span><p id="par0595" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Introduction and methodology"
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        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Diagnosis of infection and&#47;or tuberculosis disease"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Occupational hazard assessment"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Anamnesis"
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            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Specific clinical examination"
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            3 => array:3 [
              "identificador" => "sec0030"
              "titulo" => "Additional examinations"
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                0 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Tuberculin skin test"
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                1 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Interferon-gamma in vitro assays"
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                2 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Chest X-ray"
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                3 => array:2 [
                  "identificador" => "sec0050"
                  "titulo" => "Other tests"
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          "identificador" => "sec0055"
          "titulo" => "Screening for tuberculosis infection in healthcare providers"
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              "identificador" => "sec0060"
              "titulo" => "If healthcare providers already have a previous positive tuberculin test"
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            1 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "If healthcare providers already have a previous negative tuberculin test"
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            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "If healthcare providers do not have a previous tuberculin test or the result is unknown"
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              "identificador" => "sec0075"
              "titulo" => "Frequency of monitoring"
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          "identificador" => "sec0080"
          "titulo" => "Performance against accidental exposure to a patient with active tuberculosis"
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          "identificador" => "sec0085"
          "titulo" => "Performance of the Prevention Department against cases of TB or suspected TB in healthcare providers"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Period of infectiousness"
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              "titulo" => "Risk of exposure and contact study prioritization"
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                0 => array:2 [
                  "identificador" => "sec0100"
                  "titulo" => "First circle of contacts"
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                  "titulo" => "Second circle of contacts"
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                  "titulo" => "Third circle of contacts"
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          "identificador" => "sec0115"
          "titulo" => "Occupational aptitude criteria"
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          "titulo" => "General preventive measures"
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              "titulo" => "Collective measures"
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                  "titulo" => "Structural measures"
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              "titulo" => "Individual measures"
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                  "identificador" => "sec0145"
                  "titulo" => "Individual protection equipment"
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                  "titulo" => "Treatment of tuberculosis infection"
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              "titulo" => "Organizational measures"
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          "identificador" => "sec0160"
          "titulo" => "Preventive measures in special susceptibility workers"
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          "identificador" => "sec0165"
          "titulo" => "Preventive measures in pregnancy and lactation"
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        13 => array:2 [
          "identificador" => "sec0170"
          "titulo" => "Conflict of interests"
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          "identificador" => "xack214072"
          "titulo" => "Acknowledgements"
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          "titulo" => "References"
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    "fechaRecibido" => "2014-10-14"
    "fechaAceptado" => "2015-06-25"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec647754"
          "palabras" => array:3 [
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            1 => "Health care workers"
            2 => "Gamma interferon"
          ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:3 [
            0 => "Tuberculosis"
            1 => "Personal sanitario"
            2 => "Interfer&#243;n-gamma"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tuberculosis remains one of the communicable diseases that cause increased morbidity and mortality worldwide&#46; With an incidence rate of 13&#46;04 per 100&#44;000 population&#44; Spain ranks third among the most affected European countries&#46; These data show a tendency to decrease meaning that it may go unnoticed with the potential to miss the appropriate preventive measures in a suspected case&#46; In centers where patients are treated with tuberculosis&#44; health care worker presents risk of transmission&#46; This risk is higher in some areas or work units&#46; The occupational health physicians&#8217; services&#44; which monitorize the health of health care workers&#44; use different strategies in order to prevent and detect tuberculosis infection&#46; The national guidelines include the tuberculin skin test as a screening test for tuberculosis infection with mention of new diagnostic tests based on the <span class="elsevierStyleItalic">in vitro</span> detection of gamma interferon &#40;IGRA&#41; for certain cases&#46; The purpose of this guide is to establish common criteria for IGRA tests&#44; as a supplementary aid to the tuberculin skin test in health care workers&#44; from the evidence available today&#46; Recommendations for its use have been adapted to the different situations faced by the professionals involved in monitoring the health of health workers&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La tuberculosis contin&#250;a siendo una de las enfermedades transmisibles causantes de mayor morbimortalidad en el mundo&#46; Espa&#241;a con una tasa de incidencia de 13&#46;04 por 100&#46;000 habitantes ocupa el tercer lugar entre los pa&#237;ses europeos m&#225;s afectados&#46; Estos datos muestran una tendencia a su disminuci&#243;n&#44; pudiendo pasar desapercibida y hacer que no se realicen las medidas de prevenci&#243;n adecuadas ante un enfermo sospechoso&#46; El personal sanitario que trabaja en un centro donde se atiende a pacientes con tuberculosis presenta riesgo de transmisi&#243;n&#44; siendo este riesgo superior en determinadas &#225;reas o unidades de trabajo&#46; Desde los Servicios de Prevenci&#243;n de Riesgos Laborales&#44; encargados de vigilar la salud de los trabajadores sanitarios&#44; se elaboran diferentes estrategias de abordaje con el objetivo de evitar la infecci&#243;n en estos trabajadores y detectar la infecci&#243;n tuberculosa reciente&#46; Las gu&#237;as nacionales existentes hasta la actualidad incluyen la prueba de la tuberculina como prueba de cribado de la infecci&#243;n tuberculosa&#44; con referencia a las nuevas pruebas diagn&#243;sticas basadas en la detecci&#243;n <span class="elsevierStyleItalic">in vitro</span> de interfer&#243;n-gamma &#40;IGRA&#41; para determinados casos&#46; El objetivo de la presente gu&#237;a ha sido consensuar y establecer unos criterios comunes para incluir las pruebas IGRA&#44; como una ayuda complementaria a la prueba de la tuberculina en el personal sanitario&#44; a partir de la evidencia disponible en la actualidad&#46; Las recomendaciones de su utilizaci&#243;n se han adaptado a las diferentes situaciones en que se pueden encontrar los profesionales que participan en la vigilancia de la salud de los trabajadores sanitarios&#46;</p></span>"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Casas I&#44; Dominguez J&#44; Rodr&#237;guez S&#44; Matllo J&#44; Altet N&#46; Gu&#237;a para la prevenci&#243;n y control de la tuberculosis en el personal sanitario&#46; Med Clin &#40;Barc&#41;&#46; 2015&#59;145&#58;534&#46;e1&#8211;534&#46;e13&#46;</p>"
      ]
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    "apendice" => array:1 [
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        "seccion" => array:2 [
          0 => array:4 [
            "etiqueta" => "Annex I"
            "titulo" => "TST performance and interpretation procedure"
            "identificador" => "sec0175"
            "apendiceSeccion" => array:5 [
              0 => array:3 [
                "apendice" => "<p id="par0685" class="elsevierStylePara elsevierViewall">It consists of tuberculin 0&#46;1<span class="elsevierStyleHsp" style=""></span>cc intradermal injection in the ventral aspect of the forearm&#44; preferably in the left arm&#46; I is used tuberculin PPD 2 UT&#44; RT 23 or bioequivalent variety and a diluent with Tween 80&#46; It should be used an insulin type syringe and short bevel needle&#44; 26&#8211;27 gauge&#46; If administration is correct&#44; a papule emerges at the injection site&#44; which disappears in a few minutes&#46;</p>"
                "titulo" => "Mantoux technique"
                "identificador" => "sec0180"
              ]
              1 => array:3 [
                "apendice" => "<p id="par0690" class="elsevierStylePara elsevierViewall">The reading date should be the third day after administration&#44; but readings from the second to the fifth day can also be considered as valid&#46;</p>"
                "titulo" => "Reading date"
                "identificador" => "sec0185"
              ]
              2 => array:3 [
                "apendice" => "<p id="par0695" class="elsevierStylePara elsevierViewall">The margins of induration should be palpated with the index finger&#44; and good light is required&#46; Maximum margins of induration parallel to the longitudinal axis of the forearm are to be marked and induration be measured crosswise&#46; The presence of erythema alone&#44; without induration&#44; has no value&#46; Induration should be measured in mm&#44; avoiding rounding&#46;</p>"
                "titulo" => "Reading methodology"
                "identificador" => "sec0190"
              ]
              3 => array:3 [
                "apendice" => "<p id="par0700" class="elsevierStylePara elsevierViewall">No contraindications have been reported&#46; As adverse effects&#44; it rarely causes fever and malaise&#46; In the case of causing blisters&#44; these blisters should be treated as a second-degree burn&#44; once completed the test reading&#46; It can be administered to pregnant women&#46;</p>"
                "titulo" => "Contraindications and adverse effects"
                "identificador" => "sec0195"
              ]
              4 => array:3 [
                "apendice" => "<p id="par0705" class="elsevierStylePara elsevierViewall">Once open&#44; the Tuberculin containers can be used until empty&#44; regardless of the time elapsed since they began to be used&#44; provided that expiration date is not exceeded&#46; Tuberculin must always be stored in the fridge&#44; approximately at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Exposure to natural light and fluorescent light should be avoided&#46; The maximum interval between the filling of the syringe and administration is 30<span class="elsevierStyleHsp" style=""></span>min&#46;</p>"
                "titulo" => "Conservation and management of tuberculin"
                "identificador" => "sec0200"
              ]
            ]
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          1 => array:4 [
            "etiqueta" => "Annex II"
            "titulo" => "IGRA performance and interpretation procedure"
            "identificador" => "sec0205"
            "apendiceSeccion" => array:5 [
              0 => array:3 [
                "apendice" => "<p id="par0710" class="elsevierStylePara elsevierViewall">The technology involves <span class="elsevierStyleItalic">in vitro</span> stimulation of T cells with mycobacterial antigens&#44; followed by detection of IFN-&#947; produced by immunological laboratory techniques&#46; The antigens used for stimulation of T cells are specific antigens of <span class="elsevierStyleItalic">M&#46; tuberculosis</span> &#40;ESAT-6&#44; CFP-10 and TB7&#46;7&#41;&#44; but absent in BCG vaccine and most environmental mycobacteria&#46; Thus&#44; the sensitized T cells in infected individuals&#44; will release detectable amounts of IFN-&#947; after being stimulated by the specific antigens of the <span class="elsevierStyleItalic">M&#46; tuberculosis</span> complex&#46;</p>"
                "titulo" => "Theoretical basis of technology"
                "identificador" => "sec0210"
              ]
              1 => array:3 [
                "titulo" => "QuantiFERON<span class="elsevierStyleSup">&#174;</span>-Gold-In tube method"
                "identificador" => "sec0215"
                "apendiceSeccion" => array:3 [
                  0 => array:3 [
                    "apendice" => "<p id="par0715" class="elsevierStylePara elsevierViewall">For conducting both techniques a blood extraction is necessary&#46; QuantiFERON<span class="elsevierStyleSup">&#174;</span> method requires collecting blood 3<span class="elsevierStyleHsp" style=""></span>ml&#44; 1<span class="elsevierStyleHsp" style=""></span>ml inoculated in each of the 3 specific tubes for QuantiFERON<span class="elsevierStyleSup">&#174;</span>&#46; One of them contains specific antigens of <span class="elsevierStyleItalic">M&#46; tuberculosis</span> complex&#44; and the other 2 are the control tubes&#44; one of which is the positive control and one negative control&#46;</p> <p id="par0720" class="elsevierStylePara elsevierViewall">The tubes can be sent to the laboratory at room temperature&#44; or at 35<span class="elsevierStyleHsp" style=""></span>&#176;C &#40;the antigens are present inside the tube&#44; therefore&#44; stimulation is already occurring&#41;&#46; Another possibility is to incubate the tubes at 35<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; until the next day&#44; in the place of blood collection and send them to the lab next day&#46; If shipment does not take place the next day&#44; centrifuge tubes&#44; and preserve the supernatant chilled or frozen&#46; During shipment to the laboratory&#44; temperature must be the same as the sample conservation temperature&#46;</p>"
                    "titulo" => "Sample collection and transportation to the laboratory"
                    "identificador" => "sec0220"
                  ]
                  1 => array:3 [
                    "apendice" => "<p id="par0725" class="elsevierStylePara elsevierViewall">QuantiFERON<span class="elsevierStyleSup">&#174;</span>stimulates T cells present in whole blood and determines the amount of IFN-&#947; produced through ELISA&#46; In QuantiFERON<span class="elsevierStyleSup">&#174;</span>the 3 specific antigens of <span class="elsevierStyleItalic">M&#46; tuberculosis</span> &#40;ESAT-6&#44; CFP-10 y TB7&#46;7&#41; are used jointly by stimulation of whole blood&#46;</p>"
                    "titulo" => "Basis of the technique"
                    "identificador" => "sec0225"
                  ]
                  2 => array:3 [
                    "apendice" => "<p id="par0730" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 1&#44; Annex II</a>&#44; show the interpreting criteria for QFN-GIT<span class="elsevierStyleSup">&#174;</span>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>"
                    "titulo" => "Interpreting the results"
                    "identificador" => "sec0230"
                  ]
                ]
              ]
              2 => array:3 [
                "titulo" => "T-SPOT&#46;TB Technique<span class="elsevierStyleSup">&#174;</span>"
                "identificador" => "sec0235"
                "apendiceSeccion" => array:3 [
                  0 => array:3 [
                    "apendice" => "<p id="par0735" class="elsevierStylePara elsevierViewall">For T-SPOT-TB<span class="elsevierStyleSup">&#174;</span> it is necessary to collect blood 8&#8211;10<span class="elsevierStyleHsp" style=""></span>ml in CPT tube &#40;containing citrate as anticoagulant&#41; or lithium heparin tube &#40;but without separating gel&#41;&#46; The tubes can be immediately sent to the laboratory at room temperature&#46; Alternatively&#44; tubes can be incubated at room temperature until next day in darkness&#44; in the location of blood collection and subsequently be sent to a laboratory at room temperature and protected from light&#46; Once in the laboratory&#44; reagents necessary to stabilize the cells after such a long time from collection might be added to optimize the results&#46;</p>"
                    "titulo" => "Sample collection and transportation to the laboratory"
                    "identificador" => "sec0240"
                  ]
                  1 => array:3 [
                    "apendice" => "<p id="par0740" class="elsevierStylePara elsevierViewall">T-SPOT&#46;TB<span class="elsevierStyleSup">&#174;</span> requires previous separation of peripheral blood mononuclear cells &#40;PBMC&#41; for stimulation and determines the amount of T cells producing IFN-&#947; through ELISPOT&#46; In T-SPOT&#46;TB<span class="elsevierStyleSup">&#174;</span> ESAT-6 and CFP-10 antigens are used separately to stimulate PBMC&#46;</p>"
                    "titulo" => "Basis of the technique"
                    "identificador" => "sec0245"
                  ]
                  2 => array:3 [
                    "apendice" => "<p id="par0745" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 2&#44; Annex II</a>&#44; show the results&#46; The presence of reactive T cells is observed by the emergence of spots in the bottom of the well of ELISPOT&#46; These spots are counted manually and&#47;or with the help of an automatic reader&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia> <p id="par0750" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0025">Table 3&#44; Annex II</a> show the characteristics of both <span class="elsevierStyleItalic">in vitro</span> techniques of diagnosis of tuberculosis infection</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>"
                    "titulo" => "Interpreting the results"
                    "identificador" => "sec0250"
                  ]
                ]
              ]
              3 => array:3 [
                "apendice" => "<p id="par0755" class="elsevierStylePara elsevierViewall">The use of IGRA in serial screening of health workers shows a large intra-individual variation&#44; with high rates of conversions and reversals&#46; This happens because the optimal interpretation thresholds for test conversion and reversal are not well defined yet&#46; To prevent false conversions and reversals in the serial study&#44; it has been defined an area of uncertainty where the result must be considered limit and the test requires to be repeated to verify the result&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">23&#44;27</span></a></p> <p id="par0760" class="elsevierStylePara elsevierViewall">On the other hand&#44; IGRA can offer indeterminate results&#46; One possibility of indeterminate result is when the negative control obtains an abnormally high result&#44; which invalidates those obtained by the antigens and the positive control&#46; Another indeterminate result occurs when the negative control is correct&#44; the antigen control is negative&#44; but the positive control is also negative&#46; This result also invalidates the test&#44; but it can also be an indicator of lack of response of T cells of the individual&#44; and may indicate anergy and potential immunosuppression&#46; In both cases of indeterminate result&#44; repeating the determination from a new sample is recommended&#46;</p>"
                "titulo" => "Limit results and indeterminate results"
                "identificador" => "sec0255"
              ]
              4 => array:3 [
                "apendice" => "<p id="par0765" class="elsevierStylePara elsevierViewall">Although not yet fully understood&#44; it seems that the TST can also act as a stimulator of the immune response and&#44; therefore&#44; influence the results of IGRA&#44; the so-called summation reaction or booster effect which is very little likely in the negative&#44; but it is possible in the positive results&#46; To prevent this effect it is recommended that the blood is not extracted for IGRA after the third day since the tuberculin test&#46;</p>"
                "titulo" => "When performing the techniques&#63;"
                "identificador" => "sec0260"
              ]
            ]
          ]
        ]
      ]
    ]
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        "etiqueta" => "Fig&#46; 1"
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        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Performance in screening if health workers have a previous negative tuberculin skin test&#46; IGRA&#58; <span class="elsevierStyleItalic">in vitro</span> interferon-gamma release assays&#59; TST&#58; tuberculin test&#59; Rx&#58; X-ray&#59; TB&#58; tuberculosis&#59; LTBI&#58; treatment for latent TB infection&#46; &#42; &#60;35 years&#59; recent conversion&#59; immunosuppression&#59; other risk factors&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
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        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Performance in screening if the healthcare providers do not have a previous tuberculin test or the result is unknown&#46; IGRA&#58; <span class="elsevierStyleItalic">in vitro</span> interferon-gamma release assays&#59; TST&#58; tuberculin test&#59; Rx&#58; X-ray&#59; TB&#58; tuberculosis&#59; LTBI&#58; treatment for latent TB infection&#46; &#42; &#60;35 years&#59; recent conversion&#59; immunosuppression&#59; other risk factors&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Performance against occupational exposure to a case of active tuberculosis if the previous tuberculin test is negative or unknown&#46; IGRA&#58; <span class="elsevierStyleItalic">in vitro</span> interferon-gamma release assays&#59; TST&#58; Tuberculin test&#59; Rx&#58; X-ray&#59; TB&#58; tuberculosis&#59; LTBI&#58; treatment for latent TB infection&#46; &#42; &#60;35 years&#59; recent conversion&#59; immunosuppression&#59; other risk factors&#46;</p>"
        ]
      ]
      3 => array:7 [
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        "etiqueta" => "Fig&#46; 4"
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        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Performance against occupational exposure to a case of active tuberculosis if the previous tuberculin test is positive&#46; IGRA&#58; <span class="elsevierStyleItalic">in vitro</span> interferon-gamma release assays&#59; TST&#58; Tuberculin test&#59; Rx&#58; X-ray&#59; TB&#58; tuberculosis&#59; LTBI&#58; treatment for latent TB infection&#46; &#42; &#60;35 years&#59; recent conversion&#59; immunosuppression&#59; other risk factors&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
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            "Tamanyo" => 331107
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Performance on contact study jointly considering the results of the TST and IGRA&#46; IGRA&#58; <span class="elsevierStyleItalic">in vitro</span> interferon-gamma release assays&#59; TST&#58; Tuberculin test&#59; Rx&#58; X-ray&#59; TB&#58; tuberculosis&#59; LTBI&#58; treatment for latent TB infection&#59; TPTI&#58; treatment of probable tuberulosis infection&#46;</p>"
        ]
      ]
      5 => array:9 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Adapted from Jasmer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">18</span></a>"
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
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        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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                  <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="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">Groups of risk&nbsp;\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">Areas of increased risk of exposure to TB cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk factors for tuberculosis infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Immigrants from countries with a high prevalence of tuberculosis<br>&#8226; Working staff of certain centers or health facilities such as homeless shelters and prisons<br>&#8226; Voluntary workers&#44; military medical personnel&#44; taking long trips<br>&#8226; Healthcare providers assisting tuberculosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High-risk areas are microbiology laboratories&#44; units of infectious diseases&#44; the rooms for bronchoscopy or sputum inductions&#44; emergency rooms&#44; necropsy rooms and those areas where TB patients are treated<br>In areas of high risk of acquiring TB&#44; surveillance should be performed every 6&#8211;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk factors for developing tuberculosis in an infected person&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Individuals infected or recently reinfected &#40;less than 2 years&#41;<br>&#8226; People with modifications in chest X-ray showing an old untreated tuberculosis<br>&#8226; Individuals HIV coinfected<br>&#8226; People with the following comorbidities&#58; diabetes mellitus&#44; silicosis&#44; leukemia&#44; Hodgkin&#39;s disease and other lymphomas&#44; head and neck cancer&#44; lung cancer&#44; chronic renal failure&#44; gastrectomy&#44; intestinal bypass<br>&#8226; Transplated<br>&#8226; Smokers<br>&#8226; People with low weight &#40;10&#37; or over below the ideal weight&#41;<br>&#8226; People who abuse alcohol and&#47;or drugs<br>&#8226; Individuals immunosuppressed for prolonged therapy with corticosteroids&#44; chemotherapy or anti-TNF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Risk factors for tuberculosis infection and development&#46;</p>"
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      6 => array:9 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Adapted from Rodr&#237;guez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">12</span></a>"
        "detalles" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Administration of aerosolized medication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Techniques of sputum and cough induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aspiration of respiratory secretions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endotracheal intubation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bronchoscopies and endoscopies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Otolaryngological and maxillofacial examinations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Debridement and cures of tuberculous abscesses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mycobacterial sample handling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Necropsies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Tasks or techniques that increase the risk of exposure to tuberculosis&#46;</p>"
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      7 => array:8 [
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        "tabla" => array:1 [
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                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="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IFN-&#947; levels &#40;international units per ml &#91;IU&#47;ml&#93;&#41;</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">Antigens of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&nbsp;\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">Negative control &#40;Nil&#41;&nbsp;\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">Positive control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8805;0&#46;35<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;8<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;35<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;8<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8805;0&#46;5<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;35&#8211;0&#46;7<span class="elsevierStyleHsp" style=""></span>IU&#47;lml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;8<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;35<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;8<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Interpretation criteria for QFN-GIT<span class="elsevierStyleSup">&#174;</span>&#46;</p>"
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        "etiqueta" => "Table 2&#44; Annex II"
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            "identificador" => "at4"
            "detalle" => "Table 2&#44; Annex I"
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        "tabla" => array:1 [
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                  <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  " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Result&#58; spots count</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Antigens of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span></th><th class="td" title="table-head  " align="left" valign="top" scope="col">Negative control &#40;Nil&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Positive control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">ESAT-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">CFP-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">and&#47;or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8805;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">and&#47;or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8805;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">If for either or both antigens it ranges 6&#8211;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8805;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">and&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8804;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Indeterminate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">and&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Room temperature with protection from light&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Room temperature or at 35<span class="elsevierStyleHsp" style=""></span>&#176;C&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&#44; negative&#44; limit or indeterminate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#8211;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#8211;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
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          "identificador" => "bibs0005"
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              "identificador" => "bib0240"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global tuberculosis control 2012"
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                        0 => array:2 [
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                          "autores" => array:1 [
                            0 => "WHO"
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                      "Libro" => array:3 [
                        "fecha" => "2012"
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              "identificador" => "bib0245"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculosis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Zumla"
                            1 => "M&#46; Raviglione"
                            2 => "R&#46; Hafner"
                            3 => "C&#46;F&#46; von Reyn"
                          ]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra1200894"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2013"
                        "volumen" => "368"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23425167"
                            "web" => "Medline"
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                      ]
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                ]
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              "identificador" => "bib0250"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Occupational risk of tuberculosis transmission in a low incidence area"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Diel"
                            1 => "A&#46; Seidler"
                            2 => "A&#46; Nienhaus"
                            3 => "S&#46; R&#252;sch-Gerdes"
                            4 => "S&#46; Niemann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1465-9921-6-35"
                      "Revista" => array:5 [
                        "tituloSerie" => "Respir Res"
                        "fecha" => "2005"
                        "volumen" => "6"
                        "paginaInicial" => "35"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15831092"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculosis surveillance and monitoring in Europe 2012"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Dara"
                            1 => "K&#46; Kremer"
                            2 => "E&#46; Huitric"
                            3 => "C&#46; K&#246;dm&#246;n"
                            4 => "P&#46; Zucs"
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                    0 => array:1 [
                      "Libro" => array:3 [
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Instituto de Salud Carlos III&#46; Informe epidemiol&#243;gico sobre la situaci&#243;n de la tuberculosis en Espana&#46; A&#241;o 2012"
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                        0 => array:2 [
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                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2013"
                        "editorial" => "Ministerio de Sanidad&#44; Servicios Sociales e Igualdad"
                        "editorialLocalizacion" => "Madrid"
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                ]
              ]
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              "identificador" => "bib0265"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence of tuberculosis infection among healthcare workers&#58; risk factors and 20-year evolution"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Casas"
                            1 => "M&#46; Esteve"
                            2 => "R&#46; Guerola"
                            3 => "I&#46; Garc&#237;a-Oliv&#233;"
                            4 => "J&#46; Rold&#225;n-Merino"
                            5 => "C&#46; Martinez-Rivera"
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                        ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2012.12.008"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23312619"
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                  "contribucion" => array:1 [
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                      "titulo" => "Tuberculosis among health-care workers in low- and middle-income countries&#58; a systematic review"
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                          "etal" => false
                          "autores" => array:4 [
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                            2 => "D&#46; Menzies"
                            3 => "M&#46; Pai"
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                    0 => array:2 [
                      "doi" => "10.1371/journal.pmed.0030494"
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                        "tituloSerie" => "PLoS Med"
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        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0600" class="elsevierStylePara elsevierViewall">Reviewers of this guide&#58;</p> <p id="par0605" class="elsevierStylePara elsevierViewall">Albert Agull&#243;&#46; Prevention and Occupational Health Department of Deloitte &#40;Associaci&#243; Catalana de Medicina del Treball&#41; &#40;Barcelona&#41;&#46;</p> <p id="par0610" class="elsevierStylePara elsevierViewall">Luis Anibarro&#46; Tuberculosis Unit of the Pontevedra Hospital Complex&#44; Internal Medicine&#46; GEIM &#40;Study Group of mycobacterial infections of the SEIMC &#91;Spanish Society of Infectious Diseases and Clinical Microbiology&#93;&#41; &#40;Pontevedra&#41;&#46;</p> <p id="par0615" class="elsevierStylePara elsevierViewall">Vicente Arias&#46; Occupational Health Department&#44; Hospital General Universitario Gregorio Mara&#241;&#243;n &#40;Spanish Association of Specialists in Occupational Health&#41; &#40;Madrid&#41;&#46;</p> <p id="par0620" class="elsevierStylePara elsevierViewall">Vicente Ausina&#46; Microbiology Department of the Hospital Universitari Germans Trias i Pujol &#40;Badalona&#41;&#46;</p> <p id="par0625" class="elsevierStylePara elsevierViewall">Irene Barrabeig&#46; Ag&#232;ncia de Salut P&#250;blica de Catalunya&#46; Epidemiological Surveillance Unit Regi&#243; Sanit&#224;ria Barcelona-Zona Sud&#46; Generalitat de Catalunya &#40;Barcelona&#41;&#46;</p> <p id="par0630" class="elsevierStylePara elsevierViewall">Teresa del Campo&#46; Occupational Health Department and Prevention Department&#44; Fundaci&#243;n Jim&#233;nez D&#237;az&#44; Madrid&#46; &#40;Spanish Association of Specialists in Occupational Health&#41;&#46; Madrid&#46;</p> <p id="par0635" class="elsevierStylePara elsevierViewall">Joan A&#46; Cayl&#224;&#46; Epidemiology Department&#46; Ag&#232;ncia de Salut P&#250;blica de Barcelona&#46; Departament de Salut&#46; Generalitat de Catalunya &#40;Barcelona&#41;&#46;</p> <p id="par0640" class="elsevierStylePara elsevierViewall">Maria Esteve&#46; Preventive Medicine Department of the Hospital Universitari Germans Trias i Pujol &#40;Badalona&#41;&#46;</p> <p id="par0645" class="elsevierStylePara elsevierViewall">N&#250;ria Follia&#46; Ag&#232;ncia de Salut P&#250;blica de Catalunya&#46; Epidemiological Surveillance Unit Regi&#243; Sanit&#224;ria Girona&#46; Generalitat de Catalunya &#40;Girona&#41;&#46;</p> <p id="par0650" class="elsevierStylePara elsevierViewall">Joan Ingl&#233;s&#46; Occupational practitioner of the Health Surveillance Unit of Sagessa Group&#44; Hospital Universitari Sant Joan &#40;Reus&#41;&#46;</p> <p id="par0655" class="elsevierStylePara elsevierViewall">Carmen Mu&#241;oz&#46; Occupational Prevention and Safety Department at the University Hospital 12 de Octubre&#44; Madrid&#46; SERMAS &#40;Spanish Association of Specialists in Occupational Health&#41; &#40;Madrid&#41;&#46;</p> <p id="par0660" class="elsevierStylePara elsevierViewall">Silvia Nogareda&#46; Occupational Medicine &#40;Associaci&#243; Catalana de Medicina del Treball&#41; &#40;Barcelona&#41;&#46;</p> <p id="par0665" class="elsevierStylePara elsevierViewall">Juan Jos&#233; Palacios&#46; Regional Reference Unit of Mycobacteria A&#46;G&#46;C&#46; Medicine laboratory&#44; Hospital Universitario Central de Asturias&#44; GEIM &#40;Study Group of mycobacterial infections of the SEIMC &#91;Spanish Society of Infectious Diseases and Clinical Microbiology&#93;&#41; &#40;Oviedo&#41;&#46;</p> <p id="par0670" class="elsevierStylePara elsevierViewall">Anna Rod&#233;s&#46; Ag&#232;ncia de Salut P&#250;blica de Catalunya&#46; Public Health Surveillance Unit&#46; Generalitat de Catalunya &#40;Barcelona&#41;&#46;</p> <p id="par0675" class="elsevierStylePara elsevierViewall">Juan Ruiz-Manzano&#46; Microbiology Department of the Hospital Universitari Germans Trias i Pujol&#46; Member of TIR Area and PII of Tuberculosis&#46; &#40;SEPAR&#41; &#40;Badalona&#41;&#46;</p> <p id="par0680" class="elsevierStylePara elsevierViewall">Pilar Solans&#46; Territorial management of Primary Care Barcelona Ciutat de l&#8217;ICS &#40;Barcelona&#41;&#46;</p>"
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