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1.
BMC Infect Dis ; 20(1): 760, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-33059620

RESUMEN

BACKGROUND: A more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study. METHODS: We used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006-2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers' definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, 'def1') were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, 'def2'; IFN-g < 0.2 to ≥1.05 IU/ml, 'def3'; IFN-g < 0.2 to ≥1.4 IU/ml, 'def4'). Poisson regression was used for analysis. RESULTS: One thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9-32.6) using def1, 19.0 using def2 (CI:15.2-23.7), 14.7 using def3 (CI:11.5-18.8), and 12.0 using def4 (CI:9.2-15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4-0.9), in analysis including both countries. The same direction of associations were found using def 2-4. CONCLUSION: High conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis/diagnóstico , Antirretrovirales/uso terapéutico , Estudios de Cohortes , Trazado de Contacto , Composición Familiar , Seropositividad para VIH , Humanos , Incidencia , Prevalencia , Sudáfrica/epidemiología , Tuberculosis/epidemiología , Zambia/epidemiología
2.
BMC Infect Dis ; 20(1): 746, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33046016

RESUMEN

BACKGROUND: Effective active case finding (ACF) activities are essential for early identification of new cases of active tuberculosis (TB) and latent TB infection (LTBI). Accurate diagnostics as well as the ability to identify contacts at high risk of infection are essential for ACF, and have not been systematically reported from Central Asia. The objective was to implement a pilot ACF program to determine the prevalence and risk factors for LTBI and active TB among contacts of individuals with TB in Kyrgyz Republic using Quantiferon-TB Gold plus (QuantiFERON). METHODS: An enhanced ACF project in the Kyrgyz Republic was implemented in which close and household (home) contacts of TB patients from the Issyk-Kul Oblast TB Center were visited at home. QuantiFERON and the tuberculin skin test (TST) alongside clinical and bacteriological examination were used to identify LTBI and active TB cases among contacts. The association for QuantiFERON positivity and risk factors were analysed and compared to TST results. RESULTS: Implementation of ACF with QuantiFERON involved close collaboration with the national sanitary and epidemiological services (SES) and laboratories in the Kyrgyz Republic. From 67 index cases, 296 contacts were enrolled of whom 253 had QuantiFERON or TST results; of those 103 contacts had LTBI (positive TST or IGRA), and four (1.4%) active TB cases were detected. Index case smear microscopy (OR 1.76) and high household density (OR 1.97) were significant risk factors for QuantiFERON positivity for all contacts. When stratified by age, association with smear positivity disappeared for children below 15 years. TST was not associated with any risk factor. CONCLUSIONS: This is the first time that ACF activities have been reported for Central Asia, and provide insight for implementation of effective ACF in the region. These ACF activities using QuantiFERON led to increase in the detection of LTBI and active cases, prior to patients seeking treatment. Household density should be taken into consideration as an important risk factor for the stratification of future ACF activities.


Asunto(s)
Trazado de Contacto/métodos , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Pruebas Diagnósticas de Rutina , Composición Familiar , Femenino , Humanos , Lactante , Recién Nacido , Kirguistán/epidemiología , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Factores de Riesgo , Prueba de Tuberculina/métodos , Tuberculosis Pulmonar/microbiología , Adulto Joven
3.
Medicine (Baltimore) ; 99(40): e22583, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019474

RESUMEN

INTRODUCTION: Henoch-Schönlein purpura (HSP) is an extremely rare condition in patients with pulmonary tuberculosis, with only a few reported cases. Compared to patients with typical clinical symptoms, it is difficult to make a definitive diagnosis when HSP presents as an initial manifestation in pulmonary tuberculosis patients. Herein, a case of pulmonary tuberculosis that showed HSP at first was reported, and the related literatures were reviewed. PATIENT CONCERNS: A 24-year-old man presented with palpable purpura on the extremities, accompanied by abdominal pain, bloody stools, and knee pain. DIAGNOSES: The patient was diagnosed with pulmonary tuberculosis based on the results of interferon gamma release assays, purified protein derivative test, and computed tomography. INTERVENTIONS: The patient was treated with vitamin C and chlorpheniramine for 2 weeks, and the above-mentioned symptoms were relieved. However, 3 weeks later, the purpura recurred with high-grade fever and chest pain during the inspiratory phase. The patient was then treated with anti-tuberculosis drugs, and the purpura as well as the high fever disappeared. OUTCOMES: The patient recovered well and remained free of symptoms during the follow-up examination. CONCLUSION: Pulmonary tuberculosis presenting with HSP as an initial manifestation is not common. Therefore, it is difficult to clinically diagnose and treat this disease. When an adult patient shows HSP, it is important to consider the possibility of tuberculosis to avoid misdiagnosis and delayed treatment.


Asunto(s)
Antituberculosos/uso terapéutico , Púrpura de Schoenlein-Henoch/etiología , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Cuidados Posteriores , Ácido Ascórbico/uso terapéutico , Clorfeniramina/uso terapéutico , Diagnóstico Diferencial , Fiebre/diagnóstico , Fiebre/etiología , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Ensayos de Liberación de Interferón gamma/métodos , Masculino , Púrpura de Schoenlein-Henoch/tratamiento farmacológico , Resultado del Tratamiento , Tuberculina , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico por imagen , Vitaminas/uso terapéutico , Adulto Joven
4.
Brasília; CONITEC; out. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1141494

RESUMEN

INTRODUÇÃO: A ILTB é definida como um estado de resposta imune persistente à estimulação por antígenos de Mycobacterium tuberculosis sem evidência, sintomas clínicos ou achados radiológicos de doença ativa. Estima-se que um terço da população mundial possua ILTB. A importância de diagnosticar a ILTB reside no potencial de reativação para a doença ativa e transmissível quando o indivíduo estiver imunossuprimido com comorbidades ou em terapia biológica. Quando identificado o potencial de desenvolvimento de doença ativa em um indivíduo com ILTB é recomendada a realização do tratamento preconizado, de forma a impedir que ocorra a reativação. A identificação e tratamento da ILTB constituem estratégias fundamentais para reduzir a carga global de tuberculose, especialmente em países em desenvolvimento. TECNOLOGIA: Teste de liberação de interferon-gama (do inglês interferon gamma release assay - IGRA). PERGUNTAS DE PESQUISA: O uso de IGRA apresenta maior acurácia na detecção de ILTB e capacidade para prever o desenvolvimento de tuberculose ativa, em comparação ao PPD, em pacientes imunocomprometidos? EVIDÊNCIAS CLÍNICAS: Foram analisadas dez revisões sistemáticas que avaliaram o desempenho do IGRA


Asunto(s)
Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
5.
Am J Trop Med Hyg ; 103(4): 1466-1472, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32876010

RESUMEN

In many low- and middle-income countries, tuberculosis (TB) incidence in prisons is high, exposing incarcerated populations to an elevated risk of TB infection. We conducted a randomized, double-blind, placebo-controlled trial among HIV-negative male inmates of a high TB burden prison to determine whether isoniazid given twice weekly (900 mg) for 12 months prevents TB infection. The primary outcome was QuantiFERON-TB Gold in Plus (QFT) conversion to ≥ 0.35 international units per milliliter (IU/mL) at 6 months; secondary outcomes included alternative QFT thresholds (≥ 0.7, ≥ 2.0, and ≥ 4.0 IU/mL). In total, 467 participants were randomly assigned to intervention (N = 258) or control (N = 209). In an interim analysis of participants who had completed 6 months of follow-up (N = 170), QFT conversion occurred in 20.8% (19/91) and 21.5% (17/79) of participants in intervention and control arms (efficacy: 2.9%, P = 0.91), respectively. The trial was then stopped according to the trial protocol, and the remaining participants prematurely discontinued. In an analysis of secondary outcomes, the intervention arm had significantly lower rates of conversion at a cutoff of ≥ 2.0 IU/mL (efficacy: 82.6%, P < 0.01). In conclusion, 900 mg of isoniazid, administered twice a week, did not effectively prevent QFT conversion at a cutoff point ≥ 0.35 IU/mL in a trial of QFT-negative inmates. Higher QFT cutoffs are associated with sustained conversion and greater protection. Future clinical trials that evaluate protection for latent infection should use the highest cutoff than that recommended by the manufacturer.


Asunto(s)
Isoniazida , Tuberculosis Latente/tratamiento farmacológico , Prevención Primaria , Prisioneros , Tuberculosis/prevención & control , Adulto , Método Doble Ciego , Humanos , Incidencia , Ensayos de Liberación de Interferón gamma/métodos , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Tuberculosis Latente/epidemiología , Mycobacterium tuberculosis/aislamiento & purificación , Prisiones/estadística & datos numéricos , Prueba de Tuberculina/métodos , Adulto Joven
6.
Medicine (Baltimore) ; 99(36): e22015, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899054

RESUMEN

INTRODUCTION: Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. METHODS AND ANALYSIS: A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals. TRIAL REGISTRATION: Clinical-Trials.gov: NCT04236765.


Asunto(s)
Tuberculosis Latente/epidemiología , Tuberculosis Latente/transmisión , Mycobacterium tuberculosis/aislamiento & purificación , Adolescente , Niño , Pruebas Diagnósticas de Rutina/métodos , Emigrantes e Inmigrantes , Familia , Femenino , Amigos , Humanos , Incidencia , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Masculino , Mycobacterium tuberculosis/inmunología , Estudios Prospectivos , Factores de Riesgo , España/epidemiología , Viaje/tendencias , Prueba de Tuberculina/métodos
7.
PLoS One ; 15(6): e0235254, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32603343

RESUMEN

OBJECTIVE: An interferon-gamma release assay (IGRA) is used to screen for latent tuberculosis infection (LTBI). Among IGRAs, the QuantiFERON-TB Gold In-Tube (QFT-GIT) results are highly variable, so the borderline zone has been proposed to reduce unnecessary LTBI treatment. The aim of this study was to examine the proportion of the borderline zone of QFT-GIT in healthcare workers' (HCWs) serial IGRA and to retrospectively identify the utility of predicting tuberculosis (TB) in a moderate TB incidence setting. METHODS: The participants were HCWs who had undergone serial LTBI screening between June 2013 and June 2018. IGRA-positive HCWs underwent examinations that included low-dose computed tomography (LDCT) and TB culture, if necessary. Applying the borderline zone (0.2-<0.7 IU/mL), the results were classified as definite negative, borderline negative, borderline positive and definite positive. RESULTS: Through the follow-up of 477 HCWs, 441 (92.5%) invariant, 30 (6.3%) conversion, 2 (0.4%) reversion and 5 (1.0%) indeterminate results were observed with the manufacturer's cutoff. Applying the borderline zone, 419 (87.8%) invariant, 22 (4.6%) conversion, 1 (0.2%) reversion and 36 (7.5%) decision pending, including 5 (1.0%) indeterminate results, were observed. At the time of screening, five TB cases were identified. Chest X-ray (CXR) identified one TB case, and LDCT identified four additional TB cases. After one year, two TB cases were diagnosed, and their screening QFT-GIT results were definite positive and borderline negative. In the Cochran-Armitage trend test, the greater the maximum difference in the QFT-GIT grade with the borderline zone was, the higher the probability of developing TB (P-value <0.001). CONCLUSION: The application of the borderline zone lowered the conversion rate but increased the decision pending rate. Introducing the borderline zone requires a careful approach, and a thorough examination needs to be performed to rule out TB in converters. HCWs with borderline QFT-GIT results also need close observation.


Asunto(s)
Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/diagnóstico , Adulto , Femenino , Personal de Salud , Humanos , Incidencia , Ensayos de Liberación de Interferón gamma/métodos , Ensayos de Liberación de Interferón gamma/estadística & datos numéricos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis/diagnóstico , Adulto Joven
8.
BMC Infect Dis ; 20(1): 469, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32615981

RESUMEN

BACKGROUND: Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. METHODS: Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. RESULTS: Interferon gamma production was significantly higher in infected (IGRA+, n = 45) than in uninfected (IGRA-, n = 20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n = 28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively). CONCLUSION: RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Citocinas/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tamizaje Masivo/métodos , Mycobacterium tuberculosis/inmunología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Composición Familiar , Femenino , Gambia/epidemiología , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Tuberculosis Latente/microbiología , Masculino , Sensibilidad y Especificidad , Prueba de Tuberculina
9.
Medicine (Baltimore) ; 99(27): e21010, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32629720

RESUMEN

The net level of immunosuppression in kidney transplant recipients is difficult to assess. QuantiFERON Monitor (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. The aim of our study was to compare QFM testing results in stable kidney transplant recipients and kidney transplant recipients with infection, in a single-centre cohort.We enrolled 71 kidney transplant recipients from our transplantation centre. They were divided into 2 groups according to clinical presentation (Stable kidney transplant recipients or Infection).There were no significant differences in interferon-γ release between the 2 groups (Stable kidney transplant recipients 140.59 ±â€Š215.28 IU/ml, Infection group 78.37 ±â€Š197.03 IU/ml, P = .24). A further analysis revealed that kidney transplant recipients presenting with bacterial infection had significantly lower IFN-γ release when compared to stable kidney transplant recipients (26.52 ±â€Š42.46 IU/ml vs 140.59 ±â€Š215.28 IU/ml, P = .04).Kidney transplant recipients presenting with bacterial infection had lower IFN-γ release when compared to stable kidney transplant recipients. The QFM test may be useful as a tool to help guide immunosuppression dosing in kidney transplant recipients, but further studies are required to confirm its diagnostic value.


Asunto(s)
Inmunosupresión/efectos adversos , Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/sangre , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inmunidad Celular/inmunología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Receptores de Trasplantes/estadística & datos numéricos
10.
BMC Infect Dis ; 20(1): 362, 2020 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-32448123

RESUMEN

BACKGROUND: The Xpert MTB/RIF assay is an automated molecular test that is designed to simultaneously detect Mycobacterium tuberculosis (MTB) complex and rifampin resistance. However, there are relatively few studies on this method in China. Xpert has been routinely used at Peking University People's Hospital (PKUPH) since November 2016. Thus, the aim of this study was to evaluate the performance of Xpert, and provide a reference and guidance for the detection and diagnosis of TB in non-TB specialized hospitals. METHODS: The medical records of inpatients simultaneously tested with Xpert, acid-fast bacilli (AFB) smear microscopy, and interferon-gamma release assay (IGRA, by T-SPOT®.TB) at PKUPH from November 2016 to October 2018 were reviewed. Active TB cases were considered according to a composite reference standard (CRS). Then, the three methods were evaluated and compared. RESULTS: In total, 787 patients simultaneously tested with Xpert, AFB, and IGRA were enrolled; among them 11.3% (89/787) were diagnosed and confirmed active pulmonary TB (PTB, 52 cases), extrapulmonary TB (EPTB, 17 cases), and tuberculous pleurisy (TP, 20 cases). The sensitivity of Xpert in detecting PTB, EPTB, and TP was 88.5, 76.5, and 15.0%, respectively, which was slightly lower than IGRA (96.2, 82.4, and 95.0%, respectively), but higher than AFB (36.5, 11.8, and 0%, respectively); IGRA showed the highest sensitivity, but its specificity (55.9, 67.1, and 45.2%, respectively) was significantly lower than Xpert (99.6, 99.4, and 100%, respectively) and AFB (99.0, 99.4, and 100%, respectively) (P < 0.001). The sensitivity of Xpert in detecting lung tissue, cerebrospinal fluid, lymph nodes, and joint fluid was 100%, followed by sputum (88.5%), alveolar lavage (85.7%), and bronchoscopy secretion (81.2%); the pleural fluid sensitivity was the lowest, only 15.0%. For AFB negative patients, the sensitivity of Xpert in detecting PTB, EPTB, and TP was 84.9, 73.3, and 15.0%, respectively. CONCLUSIONS: Xpert showed both high sensitivity and high specificity, and suggested its high value in TB diagnosis; however, the application of pleural fluid is still limited, and should be improved. Owing to the high sensitivity of IGRA, it is recommended for use as a supplementary test, especially for assisting in the diagnosis of TP and EPTB.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Rifampin/farmacología , Tuberculosis Pleural/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , China , Femenino , Hospitales de Enseñanza , Humanos , Ensayos de Liberación de Interferón gamma/métodos , Masculino , Microscopía/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Tuberculosis Pleural/microbiología , Tuberculosis Pulmonar/microbiología , Adulto Joven
11.
J Infect Chemother ; 26(8): 818-822, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32327332

RESUMEN

The tuberculosis (TB) notification rate in Japan is gradually decreasing but has not yet achieved "pre-elimination," defined by the World Health Organization. To effectively tackle, control, and eliminate TB, estimating and monitoring the annual risk of TB infection (ARI) using tuberculin skin testing (TST) to understand the dynamics of TB epidemiology are significantly important. However, studies estimating ARIs using TST are few considering that Bacillus Calmette-Guérin vaccination coverage is high in Japan. This was a single-center, cross-sectional study conducted between January 2011 and December 2018 in Tokyo area where interferon-gamma release assays (IGRAs) were performed in newly hired researchers of Keio University School of Medicine and healthcare workers of Keio University Hospital to determine TB infection. We estimated the prevalence of TB infection and ARI based on their IGRA results. Among the 3908 subjects, 83 (2.124%) had positive IGRA results. Multiple logistic regression analysis revealed that age was a significant risk factor for positive IGRA result (adjusted odds ratio, 1.046). The ARIs were 0.049%-0.156% between 1986 and 2004, midyears of TB infection, but have not significantly decreased over approximately two decades. To decrease the risk of TB infection, advanced strategies to control and eliminate TB in Tokyo area are significantly required.


Asunto(s)
Personal de Salud/estadística & datos numéricos , Ensayos de Liberación de Interferón gamma/métodos , Investigadores/estadística & datos numéricos , Tuberculosis/epidemiología , Adulto , Factores de Edad , Anciano , Estudios Transversales , Femenino , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Prevalencia , Factores de Riesgo , Tokio/epidemiología , Tuberculosis/diagnóstico , Adulto Joven
12.
J Pediatr ; 223: 212-215.e1, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32334890

RESUMEN

In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We conducted a cross-sectional multicenter study, involving 158 children and adolescents with tuberculosis disease. The overall sensitivity of the assay was 82.9% (IQR 77.0%-88.8%), indicating that in children this test does not have higher sensitivity than previous generation interferon-gamma release assays.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Prueba de Tuberculina/métodos , Tuberculosis/microbiología
14.
Sci Rep ; 10(1): 1607, 2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-32005930

RESUMEN

Which factors are related to false negative results of the interferon-γ release assay (IGRA) is unclear. This systematic review described the risk factors associated with false negative IGRA results. Two authors independently identified studies designed to evaluate risk factors for false negative IGRA results from PubMed, the Cochrane Register of Control Trial database, and EMBASE, accessed on October 22, 2018. Meta-analyses were conducted with random-effect models, and heterogeneity was calculated with the I2 method. Of 1,377 titles and abstracts screened, 47 full texts were selected for review, and we finally included 17 studies in this systematic review. The most commonly studied risk factor (14 studies) was advanced age, followed by low peripheral lymphocyte counts (7 studies), and these factors were associated with false negative results even with different tuberculosis incidences (pooled odds ratio 2.06; 95% CI, 1.68-2.52 in advanced age and 2.68; 95% CI, 2.00-3.61 in low peripheral lymphocyte counts). Advanced age and low peripheral lymphocyte counts may be common risk factors for false negative IGRA results, suggesting that people with these factors need to be carefully followed, even if they have negative IGRA results.


Asunto(s)
Reacciones Falso Negativas , Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/metabolismo , Tuberculosis/diagnóstico , Tuberculosis/metabolismo , Humanos , Recuento de Linfocitos/métodos , Factores de Riesgo
15.
Arch Immunol Ther Exp (Warsz) ; 68(1): 4, 2020 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-32016610

RESUMEN

The number of studies which evaluated interferon-gamma release assays (IGRAs) results after anti-tuberculosis (TB) treatment has been rapidly increasing. The aim of this study was to investigate the potential use of IGRAs (QFT-GIT, T-SPOT.TB, QFT-Plus) in assessing the response to anti-TB treatment. We searched all studies in English language published from 1 October 2011 to 18 November 2018 in PubMed, Web of Science, and Scopus. Our search included the term "tuberculosis treatment AND interferon-γ release assay". We included studies evaluating the performance of commercial IGRAs (including QFT-GIT, T-SPOT.TB and QFT-Plus) before and after the anti-TB treatment. We performed subgroup analysis based on the age (children, adults), type of TB (active, latent, active and latent, and contacts exposed to MDR defined as MDR LTBI), type of IGRAs (QFT-GIT and T-SPOT.TB), and follow-up interval (2, 3, 4, 6, 9 months). Of the 18 included studies, 12 used QFT-GIT for assessment of IGRA performance after therapy, 1 used T-SPOT.TB, and 3 used both QFT-GIT and T-SPOT.TB. Since then, only two studies have assessed the QFT-Plus performance during therapy. According to the results of the meta-analysis, the pooled rate of positive IGRAs (QFT-GIT and T-SPOT.TB) following anti-TB therapy was estimated at 76% [95% CI 70-81%] and no difference was found compared to the pooled positive rate of IGRAs before initiation of therapy which was 76% [95% CI 60-89%]. The subgroup analysis showed that the pooled rate of positive IGRAs (QFT-GIT and T-SPOT.TB) after anti-TB therapy was significantly higher in monitoring active TB subjects [80% (95% CI 74-88%)] than LTBI [71% (95% CI 70-81%)]. Available data are now sufficient to suggest that monitoring changes in the IGRAs (QFT-GIT and T-SPOT.TB) response during anti-TB treatment may have limited use in evaluating the effectiveness of treatment, while the monitoring changes in QFT-Plus during anti-tubercular treatment are recommended to determine treatment efficacy or for treatment monitoring. Further research is needed to establish the efficacy of this new assay as marker on a larger scale for treatment monitoring.


Asunto(s)
Antituberculosos/uso terapéutico , Ensayos de Liberación de Interferón gamma , Tuberculosis/tratamiento farmacológico , Biomarcadores/metabolismo , Humanos , Interferón gamma/metabolismo , Ensayos de Liberación de Interferón gamma/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Juego de Reactivos para Diagnóstico , Resultado del Tratamiento , Tuberculosis/inmunología
16.
Int J Clin Pract ; 74(5): e13479, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31927772

RESUMEN

BACKGROUND: The diagnosis of tuberculous pericarditis is difficult to set, not only for its non-specific clinical presentation, but also for the lack of useful diagnostic tests. We comprehensively evaluate the overall diagnostic accuracy of Interferon-gamma release assays (IGRA) upon tuberculous pericarditis by meta-analysis. METHODS: We searched PubMed, Embase and Cochrane Library database from the earliest available date of indexing through April 30, 2019. The study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2) checklist. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-) and constructed summary receiver operating characteristic curves parameters. RESULTS: Across six results from five studies (415 patients), the pooled sensitivity for IGRA methods was 0.94 (95% confidence interval [CI]; 0.87-0.98) with heterogeneity (χ2  = 69.9, P = .01) and a pooled specificity of 0.94 (95% CI; 0.75-0.94) without heterogeneity (χ2  = 41.1, P = .13). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 16.8 (95% CI; 8.0-35.4) and negative likelihood ratio (LR-) of 0.06 (95% CI; 0.03-0.13). The pooled diagnostic odds ratio was 278 (95% CI; 114-6806). CONCLUSIONS: Interferon-gamma release assays demonstrated good sensitivity and specificity for diagnosis of tuberculous pericarditis. At present, the literature regarding remains the use of IGRA for diagnosis of tuberculous pericarditis still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of IGRA test for the diagnosis of tuberculous pericarditis.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Pericarditis Tuberculosa/diagnóstico , Humanos , Oportunidad Relativa , Curva ROC , Sensibilidad y Especificidad
17.
Medicine (Baltimore) ; 99(2): e18367, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914015

RESUMEN

Little is known about the decay kinetics of interferon (IFN)-γ response and its influencing factors in tuberculous pleurisy. We enrolled thirty-two patients with tuberculous pleurisy prospectively and followed up at month 0, 6, and 9, at which time peripheral venous blood was drawn for interferon gamma release assay (IGRA) by means of QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic and clinical data were captured. To identify significant predictive factors influencing the IFN-γ response, multiple linear regression analyses were performed. Percentage of CD4+, CD8+, Vγ2Vδ2 T cells and Treg cells were measured by flow cytometry. The percentage of QFT-GIT-positive patients at baseline, month 6 and month 9 were 96.9% (30/32), 90.6% (29/32) and 84.4% (27/32), respectively. Quantitative IFN-γ response at baseline were significantly correlated with symptom duration (P = .003, R = 0.261) and age (P = .041, R = 0.132). Besides, the decreases of the IFN-γ response at month 6 and month 9 were positively correlated with the IFN-γ level at baseline. The dynamic tendency of the percentages of Treg cells was similar to the IFN-γ responses at each time-point. Quantitative IFN-γ response could be influenced by host immune status, instead of disease burden and anti-tuberculosis treatment. IGRA is probably not a useful biomarker of treatment efficacy in tuberculous pleurisy.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/inmunología , Tuberculosis Pleural/sangre , Adulto , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Femenino , Citometría de Flujo/métodos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Linfocitos T/inmunología , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/tratamiento farmacológico , Tuberculosis Pleural/metabolismo
18.
Ann Lab Med ; 40(1): 33-39, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31432637

RESUMEN

BACKGROUND: The interferon-gamma (IFN-γ) releasing assay (IGRA) is widely used for latent tuberculosis infection (LTBI) diagnosis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based IGRA (CLIA-IGRA), AdvanSure I3 (LG Life Sciences, Seoul, Korea) and compared it with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. METHODS: Repeatability and reproducibility were evaluated at four levels. Detection capability, including limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), was evaluated using IFN-γ standard material (National Institute for Biological Standards and Control code: 87/586). Agreement between the results of two assays was evaluated using 341 blood samples from healthcare workers and patients at a tertiary care hospital. To determine the cut-off value of CLIA-IGRA for diagnosing LTBI, the ROC curve was analyzed. RESULTS: Repeatability and reproducibility were 4.86-7.00% and 6.36-7.88% CV, respectively. LoB, LoD, and LoQ were 0.022, 0.077, and 0.249 IU/mL, respectively. IFN-γ values between CLIA-IGRA and QFT-GIT showed a strong correlation within the analytical measurable range of both assays, especially when the value was low. Qualitative comparison of the two assays yielded a 99.1% overall agreement (kappa coefficient=0.98). A cut-off value of 0.35 IU/mL was appropriate for diagnosing LTBI. CONCLUSIONS: CLIA-IGRA is a reliable assay for LTBI diagnosis, with performance similar to that of QFT-GIT.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/sangre , Área Bajo la Curva , Automatización , Humanos , Inmunoensayo , Tuberculosis Latente/diagnóstico , Límite de Detección , Mediciones Luminiscentes , Curva ROC , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , República de Corea , Centros de Atención Terciaria
19.
Rheumatology (Oxford) ; 59(5): 1006-1010, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31518431

RESUMEN

OBJECTIVES: To describe the frequency of QuantiFERON-TB Gold in-tube test® (QFT-GIT) indeterminate results due to no response to phytohaemagglutinin A stimulation in the control tube in vasculitis patients prior to immunosuppressant therapy; and to compare it with other groups of patients. METHODS: This was a single-centre, retrospective study. Patients and controls were included between 1 January 2008 and 31 December 2015. We assessed the rate of indeterminate results of the QFT-GIT in 38 patients with systemic vasculitis prior to any corticosteroid or immunosuppressant therapy, compared with 40 non-vasculitis patients with biological inflammatory syndrome, and 310 non-immunosuppressed patients matched for gender and age. RESULTS: Indeterminate results due to no response to phytohaemagglutinin A were more frequent in vasculitis patients (21.1%) compared with non-vasculitis patients with biological inflammatory syndrome (7.5%) (Fisher's exact test: P = 0.11) and to anonymized controls (7%) (P = 0.009). Responses to phytohaemagglutinin A were significantly lower in vasculitis patients compared with other groups (Kruskal-Wallis test: P < 0.0001) and compared with non-vasculitis patients with biological inflammatory syndrome (P = 0.0015). The multivariable analysis identified as independent predictors of an indeterminate result of the QFT-GIT: the presence of systemic vasculitis (odds ratio 9.64 [1.14-81.3], P = 0.037) and a high neutrophil-to-lymphocyte ratio (odds ratio 1.70 [1.21-2.37], P = 0.002). One patient with an indeterminate result of QFT-GIT developed active tuberculosis after one year of corticosteroid therapy for giant cell arteritis. CONCLUSION: Our results question the reliability of QFT-GIT to rule out latent tuberculosis in vasculitis patients at diagnosis, prior to immunosuppressant therapy.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/microbiología , Prueba de Tuberculina/métodos , Corticoesteroides/administración & dosificación , Adulto , Factores de Edad , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Humanos , Inmunosupresión/métodos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mycobacterium tuberculosis/aislamiento & purificación , Valor Predictivo de las Pruebas , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales
20.
J Infect Chemother ; 26(2): 194-198, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31495568

RESUMEN

OBJECTIVES: The interferon-gamma release assay (IGRA) is useful for diagnosing Mycobacterium tuberculosis infections, especially in countries where Bacille Calmette-Guérin vaccinations are performed. However, reproducibility of the IGRA is unclear, as recent data suggest high IGRA conversion and reversion rates in serial tests among healthcare workers. This longitudinal study aimed to evaluate reproducibility of T-SPOT.TB for screening M. tuberculosis infections in Japan. METHODS: Results of T-SPOT.TB tests performed between April 2014 and March 2016 at two hospitals in Yokohama, Japan, where the incidence of tuberculosis was 18.0 per 100,000 population in 2014, were analyzed. RESULTS: In total, 3890 T-SPOT.TB tests were included. Overall, positive and negative test rates were 8.4% and 87.6%, respectively. Among 373 serial tests within two years, conversion and reversion rates were only 1.1% and 12.5%, respectively. Almost all patients who were initially negative (98.9%) remained so. There was no statistically significant difference between the outcomes observed at the two hospitals. CONCLUSIONS: The conversion rate of T-SPOT.TB in Japan is as low as that recently reported in other countries where the incidence of tuberculosis is low. These data indicate that T-SPOT.TB is a reproducible tuberculosis screening tool at local hospitals in areas with a moderate incidence of tuberculosis.


Asunto(s)
Ensayos de Liberación de Interferón gamma/normas , Mycobacterium tuberculosis/inmunología , Tuberculosis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Ensayos de Liberación de Interferón gamma/métodos , Japón , Estudios Longitudinales , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Reproducibilidad de los Resultados , Prueba de Tuberculina/normas , Tuberculosis/microbiología , Adulto Joven
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