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OBJECTIVES: To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. METHODS: A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). RESULTS: QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. CONCLUSIONS: The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context.

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Background: Healthcare workers (HCWs) have a higher risk of latent tuberculosis infection (LTBI) and active tuberculosis than the general population. In HCWs, the risk of tuberculosis infection depends on the local tuberculosis prevalence, HCWs' characteristics, the healthcare facility, and prevention and control measures. We aimed to estimate the prevalence and risk factors for LTBI in HCWs at a northern Peruvian hospital. Methods: This study had two phases: (1) a cross-sectional phase involving recruitment, history taking, and sampling for the Interferon-Gamma Release Assays (IGRA test), and (2) a prospective follow-up of IGRA-positive participants. We enrolled direct and non-direct patient caregivers among HCWs. We defined an LTBI case if the IGRA test was positive and clinical, laboratory, and radiological evaluations for active tuberculosis were negative. Results: We recruited 308 participants between November 2022 and May 2023. The mean age was 38.6 ± 8.3 years. Over 75% of the participants were female. The most common job category was technicians (30.5%), physicians (22.7%), nurses (20.5%), and other HCWs groups (17.5%). Most participants worked in hospital wards (28.2%), diagnostics departments (16.9%), and critical care departments (15.6%). The LTBI prevalence among HCWs was 17.86% (95% CI 13.84-22.70). In multivariate analysis, after adjusting for age, time working in our hospital, and family history of tuberculosis, males had a higher risk of LTBI (aPR 1.69, 95% CI 1.01-2.77) than females. Working for more than 10 years increased the risk of LBTI (aPR 2.4, 95% CI 1.44-3.97) compared to working for ≤10 years. Even further, participants who had worked for more than 20 years had an aPR of 4.31 (95% CI 1.09-13.65) compared to those with ≤10 years. Similarly, occupational exposure increased the risk of LTBI (aPR 2.21, 95% CI 1.27-4.08) compared to those HCWs not occupationally exposed. Conclusion: The LTBI prevalence in HCWs at a northern Peruvian hospital was lower compared to other Peruvian cities. Males, more experienced, and occupational exposed HCWs are at higher risk of LTBI. LTBI prevalence in Peruvian HCWs is still high. More studies are needed to address some aspects this study has not examined.

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INTRODUCTION: Patients with rheumatoid arthritis (RA) are at increased risk of developing tuberculosis, and even more so if they receive biological agents. In Mexico, the prevalence of latent tuberculosis infection (LTBI) in RA diagnosed by interferon-gamma release assay (IGRA) is largely unknown. The objective was to determine LTBI prevalence and the associated risk factors in rheumatoid arthritis patients. METHODS: A cross-sectional study was performed comprising 82 patients with RA who attended the rheumatology service at a second-level hospital. Demographic characteristics, comorbidity, Bacillus Calmette-Guerin (BCG) vaccination and smoking history, type of treatment, disease activity and functional capacity were investigated. The Disease Activity Score 28 and the Health Assessment Questionnaire-Disability Index were applied for the estimate of RA activity and functional capacity. Further information was compiled from the electronic medical records and personal interviews. LTBI was determined by QuantiFERON TB Gold Plus (QIAGEN, Germantown, USA). RESULTS: Prevalence of LTBI was 14% (95% confidence interval (CI): 8.6% to 23.9%). Factors associated with LTBI were history of smoking (odds ratio (OR) = 6.63 95% CI 1.01 to 43.3) and disability score (OR = 7.19 95%CI 1.41 to 36.6). CONCLUSIONS: The prevalence of LTBI in Mexican patients with RA was 14%. Our results suggest prevention of smoking and functional incapacity could reduce the risk of LTBI. Further research could endorse our results.

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The aim of this study was to evaluate the prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation candidates, using tuberculin skin test and QuantiFERON-TB Gold-Plus, in a high-burden tuberculosis country. Adult candidates for hematopoietic stem cell transplantation performed both tests before and those submitted to transplantation were followed up for 12 months. The prevalence of latent Mycobacterium tuberculosis infection was 17.1% and a moderate agreement between QuantiFERON-TB Gold-Plus and tuberculin skin test was observed in this population. Previous tuberculosis exposure was a risk factor for latent Mycobacterium tuberculosis infection. No cases of tuberculosis were diagnosed during follow-up period.

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La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

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Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.

Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.

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Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.

Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.

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ABSTRACT Objective: To evaluate the frequency of and factors associated with indeterminate interferon-gamma release assay (IGRA) results in people living with HIV/AIDS (PLWHA). Methods: We tested 81 PLWHA in the central-west region of Brazil, using the tuberculin skin test and an IGRA. Information on sociodemographic and clinical variables was gathered through the use of questionnaires and from medical records. The association of those variables with indeterminate results was analyzed by calculating the adjusted ORs in a multivariate logistic regression model. Concordance was evaluated by determining the kappa statistic. Results: Among the 81 patients evaluated, the tuberculin skin test results were positive in 18 (22.2%) of the patients, and the IGRA results were positive in 10 (12.3%), with a kappa of 0.62. The IGRA results were indeterminate in 22 (27.1%) of the patients (95% CI: 17.8-38.1%). The odds of obtaining indeterminate results were significantly higher in smokers (adjusted OR = 6.0; 95% CI: 1.4-26.7) and in samples stored for less than 35 days (adjusted OR = 14.0; 95% CI: 3.1-64.2). Patients with advanced immunosuppression (CD4+ T-cell count < 200 cells/mm3) were at a higher risk for indeterminate results (OR adjusted for smoking and inadequate duration of sample storage = 4.7; 95% CI: 0.91-24.0), although the difference was not significant. Conclusions: The high prevalence of indeterminate results can be a major limitation for the routine use of IGRAs in PLWHA. The need to repeat the test increases its costs and should be taken into account in cost-effectiveness studies. The processing of samples can significantly alter the results.

RESUMO Objetivo: Avaliar a frequência de resultados indeterminados de um interferon-gamma release assay (IGRA, ensaio de liberação de interferon-gama) e os fatores relacionados com esses resultados em pessoas vivendo com HIV/AIDS (PVHA). Métodos: Foram avaliadas 81 PVHA na região Centro-Oeste do Brasil, por meio do teste tuberculínico e de um IGRA. Informações a respeito de variáveis sociodemográficas e clínicas foram obtidas por meio de questionários e prontuários médicos. A relação entre essas variáveis e os resultados indeterminados foi avaliada por meio do cálculo da OR ajustada em um modelo de regressão logística multivariada. A concordância foi avaliada por meio do coeficiente kappa. Resultados: Os resultados do teste tuberculínico e do IGRA foram positivos em 18 (22,2%) e 10 (12,3%), respectivamente, dos 81 pacientes avaliados (κ = 0,62). O resultado do IGRA foi indeterminado em 22 (27,1%) dos pacientes (IC95%: 17,8-38,1%). A chance de resultados indeterminados foi significativamente maior em fumantes (OR ajustada = 6,0; IC95%: 1,4-26,7) e em amostras armazenadas durante menos de 35 dias (OR ajustada = 14,0; IC95%: 3,1-64,2). Pacientes com imunossupressão avançada (contagem de células T CD4+ < 200 células/mm3) apresentaram maior risco de resultados indeterminados (OR ajustada para tabagismo e tempo inadequado de armazenamento das amostras = 4,7; IC95%: 0,91-24,0), embora a diferença não tenha sido significativa. Conclusões: A alta prevalência de resultados indeterminados pode ser um grande obstáculo ao uso rotineiro de IGRAs em PVHA. A necessidade de repetir o teste aumenta seu custo e deve ser levada em conta em estudos da relação entre custo e eficácia. O processamento das amostras pode alterar significativamente os resultados.

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A great diversity of infectious agents can affect patients that use steroids at immunosuppressive doses or tumor necrosis factor α (TNF-α) antagonists. The list of participating microorganisms is more restricted in the case of anti TNF-α blockers. Overlapping agents include intracellular bacteria, Mycobacterium tuberculosis, geographic fungal agents that have the ability to establish granulamotous infections, herpes zoster, and reactivation of chronic hepatitis B virus infection. An important conceptual issue for these infections is the existence of a threshold prednisone daily dose for the emergence of opportunistic infections but higher levels of immunosuppression and cofactors are required in the case of Pneumocystis jiroveci and cytomegalovirus infections. In order to prevent these threats, a detailed medical evaluation is needed before prescription to detect potential risks and manage them properly. Prevention rules must be prescribed in every case, that include common sense behaviors, vaccines, and in selected cases, chemoprophylaxis for latent tuberculosis (TB) infection, P. jiroveci pneumonia (PCP) or other specific requirements. Latent TB infection is probable and requires chemoprophylaxis in the case of remote or recent exposure to a patient with lung TB, a positive tuberculin or interferon-gamma release assay result or residual lung scars in a chest x-ray exam. PCP prevention is suggested when the patient reaches a daily dose of prednisone of 30 mg but might be needed at lower doses in case of other concomitant immunosuppressive drugs or when lymphopenia arises shortly after prednisone initiation.

Una gran diversidad de agentes infecciosos puede afectar a los pacientes que usan corticosteroides en dosis inmunosupresoras o antagonistas del factor de necrosis tumoral o (FNTα). La lista de microorganismos participantes es más restringida en el caso de los bloqueadores del FNTα. Los agentes que se sobreponen incluyen bacterias intracelulares, Mycobacterium tuberculosis, hongos geográficos que son capaces de establecer infecciones granulomatosas, herpes zoster y reactivación de hepatitis crónica por virus de hepatitis B. Existe una dosis umbral diaria de prednisona (o equivalente), sobre la cual emergen estas infecciones oportunistas, pero el nivel de inmunosupresión parece ser más alto en el caso de Pneumocystis jiroveci o citomegalovirus. Para prevenir estas amenazas, se requiere una evaluación médica detallada antes de su prescripción para detectar riesgos potenciales y manejarlos apropiadamente. Se deben indicar medidas de prevención en cada caso, las que incluyen conductas de sentido común y en casos seleccionados, quimioprofilaxis para infección latente por tuberculosis (TBC), neumonía por P. jiroveci u otros requerimientos específicos. La existencia de TBC latente es probable en el caso de exposición reciente o remota a un bacilífero pulmonar, prueba de tuberculina o de liberación de interferón γ positiva, o lesiones residuales en la radiografía de tórax. La prevención de neumonía por P. jiroveci se recomienda cuando se usan al menos 30 mg de prednisona al día pero puede ser necesario a dosis menores si se aplican otros fármacos inmunosupresores concomitantes o si aparece linfopenia poco después del inicio de los corticosteroides.

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INTRODUÇÃO: O fato do vírus da Hepatite C (HCV) estabelecer uma infecção crônica persistente, na maioria dos casos, mesmo sendo reconhecido e alvejado pelos sistemas imune inato e adaptativo sugere que o mesmo tenha desenvolvido estratégias eficazes para driblar a ação desses sistemas. O HCV interfere na fase inicial de ativação da resposta imune adaptativa alterando a função das células dendríticas (DCs), o que provavelmente leva a uma ativação deficiente das células natural killer (NKs) e de linfócitos T. Portanto, a realização de estudos sobre DCs e NKs na infecção pelo HCV se torna de fundamental importância para a compreensão da patogênese e persistência desta infecção. MÉTODOS: Foram selecionados indivíduos com resolução espontânea da infecção pelo HCV, indivíduos com infecção crônica e indivíduos saudáveis. A técnica de citometria de fluxo foi utilizada para a determinação da frequência e do fenótipo de células dendríticas e NKs nesses indivíduos. Além disso, foi avaliada a atividade citotóxica das células NKs sob estímulo de IL-12 e IL-18, e também da linhagem K-562. RESULTADOS: A frequência de DC mielóides (mDC) expressando CD86, nos indivíduos crônicos, foi elevada e uma correlação positiva com a carga viral foi observada. Na análise do ensaio funcional foi observado que as populações de células NKs CD7+ CD57+ apresentaram maior expressão da molécula CD107a e baixa produção de IFNy nos indivíduos com infecção crônica. A constante exposição das células imunes ao IFN-alfa, induzido durante a infecção pelo HCV, resulta na polarização do fenótipo citotóxico, caracterizado por células NK ativadas com elevado poder de degranulação, mas com deficiente produção de IFN-y. CONCLUSÕES: As frequências das células DCs e NKs eram semelhantes em todos os indivíduos. A expressão da molécula CD86 na superfície das mDCs pode ter sido induzida pela presença do HCV, uma vez que foi observada correlação positiva com a carga viral...

INTRODUCTION: Hepatitis C virus (HCV) develops a chronic persistent infection in most of the cases, even being recognized and targeted by the innate and adaptive immune systems, suggests that the virus have developed effective strategies to circumvent the action of these systems. HCV interferes in the initial activation of the adaptive immune response by altering the function of dendritic cells (DCs), which probably leads to a deficient activation of natural killer cells (NK) and T lymphocytes. Therefore, studies of DCs and NK in HCV infection are very important for understanding the pathogenesis and the persistence of this infection. METHODS: We selected subjects with spontaneous resolution of HCV infection, with chronic infection and healthy subjects. Flow Cytometry was used to determine the frequency and phenotype of dendritic cells and NK cells of these individuals. In addition, we evaluated the NK cell cytotoxic activity in response to stimulation of IL-12 and IL-18 and in co-cultivation with the cell line K-562. RESULTS: In individuals with chronic infection, the frequency of myeloid (m) DC cells expressing CD86 was elevated and a positive correlation between these cells and viral load was observed. It was observed in chronic infected individuals that NK cells co-expressing CD7 and CD57 showed higher expression of CD107a and low production of IFN gamma. The constant exposure of immune cells to IFN-alfa induced during HCV infection results in the polarization of cytotoxic phenotype characterized by activated NK cells with high power degranulation, but with impaired production of IFN-y. CONCLUSIONS: The frequency of DCs and NK cells were similar in all individuals. The expression of CD86 molecule on the surface of mDCs may have been induced by the presence of HCV, since a positive correlation was observed with viral load. Cytotoxic NK cells, highly differentiated and unable to produce IFN-y, were the most frequent in chronic HCV infection...

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