ABSTRACT
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.
Subject(s)
Humans , Latent Tuberculosis/drug therapy , Rifamycins/therapeutic use , Tuberculosis/prevention & control , Tuberculin Test , Latent Tuberculosis/diagnosis , Interferon-gamma Release Tests , Isoniazid/therapeutic use , Antitubercular Agents/therapeutic useABSTRACT
Resumo A detecção precisa da infecção latente por tuberculose está se tornando cada vez mais importante devido ao aumento do uso de medicamentos imunossupressores e da epidemia do vírus da imunodeficiência humana, o que aumentou o risco de reativação à tuberculose ativa (TB). O Teste IGRA QuantiFERON® TB Gold apresenta vantagens frente ao teste de PPD como por exemplo, requer somente uma coleta de amostra sanguínea ; não há necessidade que o paciente retorne ao laboratório para leitura e interpretação dos resultados; Os resultados são objetivos, não requerem interpretação do leitor ou interferência de critérios subjetivos; trata-se de um teste in vitro, portanto não há "efeito booster" (potenciação da reação tuberculínica); o teste não é afetado por vacinação prévia por BCG ou infecção por outras espécies de micobactérias. Limitações são descritas, apesar de raras, como reações cruzadas deste método com infecções por algumas espécies de micobactérias não-tuberculosis (incluindo Mycobacterium kansasii, Mycobacterium szulgai e Mycobacterium marinum). Ainda há poucos dados sobre o teste IGRA em certas populações, como por exemplo, em crianças, pacientes imunocomprometidos e mulheres grávidas. Nestes grupos, a interpretação do teste pode ser difícil e mais estudos se fazem necessários.
Abstract Precise detection of latent tuberculosis infection is becoming increasingly important due to increased use of immunosuppressive drugs and the human immunodeficiency virus epidemic , which increased the risk of reactivation to active tuberculosis (TB).The QuantiFERON® TB Gold IGRA Test has advantages over the skin test for TB, otherwise known as a Mantoux tuberculin test, for example, requires only a blood sample collection; there is no need for the patient to return to the laboratory for reading and interpretation of the results; The results are objective, do not require interpretation of the reader or interference of subjective criteria; it is an in vitro test, so there is no "booster effect" (potentiation of the tuberculin reaction); the test is not affected by prior BCG vaccination or infection with other species of mycobacteria. Limitations are described, although rare, as cross-reactions of this method with infections by some species of non-tuberculosis mycobacteria (including Mycobacterium kansasii, Mycobacterium szulgai and Mycobacterium marinum). There is still little data on the IGRA test in certain populations, such as in children, immunocompromised patients and pregnant women. In these groups, the interpretation of the test can be difficult and more studies are needed.
Subject(s)
Humans , Uveitis/diagnosis , Tuberculin Test , Tuberculosis, Ocular/diagnosis , Interferon-gamma Release Tests/methods , Tuberculin/analysis , Comparative Study , Interferon-gamma/analysis , Mycobacterium tuberculosis/isolation & purificationABSTRACT
A 46 year old Iraqi Kurd female patient was presented with recurrent round erythematous skin lesions on her upper and lower extremities mainly calves, lower abdomen, and buttock for 3 years. Routine laboratory investigations were unremarkable; however, based on strongly positive tuberculin skin test, positive interferon gamma release assay, histo-pathological findings and a response to anti-TB treatment, she was diagnosed with Erythem Induratum of Bazin (EIB). The patient was treated successfully with combination anti-TB drugs. The skin lesions disappeared after 2 months of the treatment. There was no recurrence of the lesions over a 6 month follow up period.
ABSTRACT
PURPOSE: This study aimed to evaluate ichroma™ IGRA-TB, a novel point-of-care platform for assaying IFN-γ release, and to compare it with QuantiFERON-TB Gold In-Tube (QFT-GIT) for identifying Mycobacterium tuberculosis (M. tb) infection. MATERIALS AND METHODS: We recruited 60 healthy subjects, and blood samples were obtained in QFT-GIT blood collection tubes. The blood collection tubes were incubated at 37℃, and culture supernatant was harvested after 18–24 hours. IFN-γ responses were assessed by the ichroma™ IGRA-TB cartridge and the QFT-GIT IFN-γ enzyme-linked immunosorbent assay. Three active TB patients were recruited as a positive control for M. tb infection. RESULTS: The area under the receiver operating characteristic curve of the ichroma™ IGRA-TB test for differentiating between infected and non-infected individuals was 0.9706 (p < 0.001). Inconsistent positivity between the two tests was found in three participants who showed weak positive IFN-γ responses ( < 1.0 IU/mL) with QFT-GIT. However, the two tests had excellent agreement (95.2%, κ=0.91, p < 0.001), and a very strong positive correlation was observed between the IFN-γ values of both tests (r=0.91, p < 0.001). CONCLUSION: The diagnostic accuracy demonstrated in this study indicates that the ichroma™ IGRA-TB test could be used as a rapid diagnostic method for detecting latent TB infection. It may be particularly beneficial in resource-limited places that require cost-effective laboratory diagnostics.
Subject(s)
Humans , Diagnosis , Enzyme-Linked Immunosorbent Assay , Feasibility Studies , Healthy Volunteers , Korea , Latent Tuberculosis , Methods , Mycobacterium tuberculosis , Point-of-Care Systems , ROC Curve , TuberculosisABSTRACT
Objective To investigate the Mycobacterium tuberculosis infections in 2014 among Beijing army recruits, and evaluate a new method for screening latent tuberculosis infections.Methods A total of 194 army recruits were subjected to chest X-ray examination purified protein derivative(PPD) skin test, antibody detection, and interferon gamma release assay(IGRA) by ELISA combined with recombinant protein CFP10-ESAT6 and latent infection protein Rv2628.Results The positive rates of PPD skin test and antibody test were 49.7% and 15.5%, respectively.The latent infection rate of IGRA test was 22.2% in 194 cases after CFP10-ESAT6 stimulation.After stimulation of latent tuberculosis infection(LTBI) with Rv2628, IFN-γ level was significantly higher than that in healthy control group (P0.05).There was no significant difference between antibody negative and positive groups after stimulation by CFP10-ESAT6 and Rv2628 (P>0.05).The area under the ROC curve of Rv2628 diagnosis of tuberculosis infection was 0.84.When Youden index was 0.621,the specificity was 94.7% and sensitivity was 67.4%.ConclusionCombined detection of antigens Rv2628 and CFP10-ESAT6 specific IFN-γ values can be potentially used for differential diagnosis of active or latent tuberculosis infections.
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Background & objectives: Tuberculosis (TB) is a common infection in patients on haemodialysis. There is a definite role of treatment of latent TB (LTB) in these patients. However, diagnosis of LTB in these patients by tuberculin skin test (TST) is unreliable. There is suggestion that interferon gamma release assay (IGRA) will be more reliable test for diagnosis of LTB in this setting. Thus, we evaluated value of IGRA and TST for the diagnosis of LTB in patients on dialysis in an Indian setting. Methods: Patients with end stage kidney disease on dialysis were included. Patients with active TB were excluded. Each patient was subjected to TST (induration of ≥10 mm was taken as positive) and QuantiFERON TB Gold In-Tube test (QFT-GIT) for diagnosis of LTB. Results: A total of 185 patients were included; 129 (69.7%) were males and mean age was 36.7 ± 12.3 yr. Past history of TB was present in 18 (9.7%) patients. One hundred and thirty four (72.4%) patients had scar of BCG vaccination. QFT-GIT test was positive in 66 (36%), TST in 32 (17%) and both in 13 (7%) patients. Of the 66 patients positive with QFT-GIT, only 13 (19.6%) were positive for TST. Of the 32 patients positive with TST, only 13 (40.6%) were positive with QFT-GIT; 100 (54%) patients were negative for both the tests. Overall, 85 (45.9%) patients were positive for either of the two tests. Poor agreement was shown between the two methods. On logistic regression analysis, odds of QFT-GIT to be positive in patients with BCG vaccination was 1.23 and with history of TB 0.99, both being insignificant. odds of tuberculin skin test to be positive in patients with BCG vaccination was 1.04 and with history of TB 0.99, both again being insignificant. Interpretation & conclusions: Our findings showed that more number of patients (36%) on haemodialysis were positive for QuantiFERON Gold In-Tube test as compared to TST (17%). There was poor agreement between the two tests. no significant effect of BCG vaccination and history of TB in past was observed on both tests.
ABSTRACT
Objective To study the feasibility of in vitro release of γ-interferon tests (IGRA) in screening of tuberculosis for children with close TB contacts. Methods 185 children with close TB contacts were detected by IGRA at the pediatric clinic in our hospital. Results In IGRA-positive group, the rate of strong positive PPD (PDD≥15 mm) was 50.9%, which was higher than 9.1% in IGRA-negative group (X2 =37.263, P < 0.00). The morbidity rate for children with close TB contacts was 30.2% in IGRA-positive group, and it was significantly higher than 3.0% in IGRA-negative group (X2 = 28.928, P < 0.00). The sensitivity was 80% and the specificity was 77.6% for IGRA screening in children who had close contacts with TB patients. The sensitivity would be 95.0%, as the test was combined with PPD test. Conclusions IGRA screening in children with close TB contacts can increase the detection rate of tuberculosis and reduce imaging screening.
ABSTRACT
Objective To evaluate the advantages of TB-IGRA and protein chip to detect the Mycobacterium tuberculosis. Methods From October 2013 to March 2014,collected 78 cases of clinical diagnosis of tuberculosis and normal control’s pe-ripheral blood specimens,used TB-IGRA kits and Mycobacteriumtuberculosis IgG kit(protein chip)to detected respectively. The results were analyzed and compared.Results The sensitivity of protein chip and TB-IGRA in the detection of Mycobac-teriumtuberculosis were 34.5% and 89.7% respectively,which was statistically significant (χ2=26.95,P 0.05).The positive rate of TB-IGRA and Protein chip in tuberculosis were 90.5% and 42.9%.The positive rate of TB-IGRA and Protein chipin extrapulmonary tuberculosis were 89.20% and 29.7% respectively.Conclusion Compared TB-IGRA and protein chip,either diagnose tuberculosis or extrapulmonary tuberculosis has highly positive rate and sensitivity, TB-IGRA can be widely used in the early screening of tuberculosis.
ABSTRACT
O diagnóstico laboratorial da tuberculose é de fundamental importância para o correto tratamento e controle da disseminação da doença. Dentre os principais métodos diagnósticos, os testes baseados em biologia molecular vêm ocupando cada vez mais um papel de destaque; entretanto, ainda não substituem por completo os métodos tradicionais, como a cultura e a pesquisa direta. A dosagem da adenosina deaminase (ADA) tem utilidade no diagnóstico de doença extrapulmonar e o teste de liberação de interferon gama linfocitário (IGRA) é de utilidade no diagnóstico de tuberculose latente. A utilização conjunta dos diferentes métodos disponíveis tem trazido grandes vantagens clínicas
The laboratory diagnosis of tuberculosis is of fundamental importance for the correct treatment and control the spread of the disease. Among the main diagnostic methods, the tests based on molecular biology are occupying an increasingly prominent role, however, has not yet completely replace traditional methods such as culture and direct search. The determination of adenosine deaminase (ADA) has useful in diagnosis of extrapulmonary disease and the interferon gamma release assay (IGRA) is useful in the diagnosis of latent tuberculosis. The combination use of different methods available has brought great clinical advantages
Subject(s)
Humans , Male , Female , Latent Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosis , Adenosine Deaminase/analysis , Staining and Labeling/methods , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/isolation & purification , Polymerase Chain Reaction/methods , Bacteriological Techniques/methods , Interferon-gamma Release TestsABSTRACT
A review of the epidemiology of tuberculosis, its contributing risk factors (excluding HIV) and the role of screening latent tuberculosis infection in Malaysia was done. Despite the global and domestic decrease in prevalence rates of tuberculosis in the past decade, there is an alarming increase in the trend of non communicable diseases in the country. High prevalence rates of major risk factors leading to reactivation of tuberculosis were seen within the population, with diabetes mellitus being in the forefront. The rising numbers in the ageing population of Malaysia poses a further threat of re-emergence of tuberculosis in the years to come. Economically, screening of diabetic patients with comorbidities for latent tuberculosis infection (LTBI) using two major techniques, namely tuberculin sensitivity (TST) and Interferon gamma release assay tests (IGRA) could be a viable option. The role of future research in the detection of LTBI in the Malaysian setting might be necessary to gauge the disease reservoir before implementing prophylactic measures for high risk groups involved.
ABSTRACT
Tuberculosis (TB) is a main cause of disease and death in many countries of the world. The efforts to control this scourge have not been very successful. Even in Chile where we are near to reach the advanced stage of elimination of TB as a public health problem, five persons each week die of this disease. The main challenges for the control of TB and the most recent advances to counteract them are reviewed. A series of modern methods of diagnosis based on the techniques of molecular biology are reviewed. There is a need to develop procedures that can be applied in the so called "point of diagnosis", like the Xpert MTB/RIF test. There are new techniques for the diagnosis of latent TB infection (IGRA's), in order to identify infected subjects of high risk to develop disease to subject them to chemo-profilaxis. We need to develop shorter treatments for new cases and better drugs for multi-resistant patients. Ten new drugs have progressed into the clinical development pipeline for TB. New vaccines against tuberculosis are being investigated. Some of them are already being tried in the field. In the last years two new challenges have appeared: the association TB-AIDS, and the new epidemics of Multi Drug Resistant Tuberculosis (TB MDR and TB XDR). New techniques of diagnosis are described. Our main challenge is to make all this advances available for everybody. In Chile only the private sector has some of these techniques.
La tuberculosis (TBC) sigue siendo una de las principales causas de morbi-mortalidad en el mundo y los esfuerzos para controlarla han demostrado ser insuficientes. Aun en Chile, donde estamos cerca de alcanzar la etapa avanzada de su eliminación como problema de salud pública, fallecen 5 personas por semana de TBC. Este artículo presenta los principales desafíos de los Programas de Control de la TBC y los avances más recientes para enfrentarlos. Se analiza una serie de métodos de diagnóstico basados en técnicas de biología molecular. Se necesitan técnicas más sensibles que la baciloscopia que puedan ser empleadas en la periferia, en el llamado "punto del diagnóstico", como el test Xpert MTB/RIF. Están en estudio nuevos métodos de diagnóstico de la infección tuberculosa latente -los IGRA's - para identificar con mayor especificidad que con el PPD, a los infectados con alto riesgo de progresar a TBC para someterlos a quimioprofilaxis. Necesitamos tratamientos más breves para los casos nuevos, y drogas más eficaces para los enfermos de TBC multi-resistentes. Está en desarrollo la introducción de 10 nuevos medicamentos anti-TBC. Se necesitan vacunas más eficaces que la BCG, capaces no sólo de prevenir la infección, sino también de reforzar la inmunidad de los infectados y aún de los enfermos. Varias de estas vacunas se están ensayando en África. En los últimos decenios han aparecido dos nuevos desafíos: la asociación TBC-SIDA y las epidemias de TBC multi-resistentes (TB MDR y XDR). Se han desarrollado técnicas para identificar polimorfismos del gen rpo B, principal causa de resistencia a la rifampicina, considerada marcador de TB MDR. El principal desafío actual es poner todos estos avances al alcance de los que más los necesitan. En Chile sólo disponemos de algunas de estas nuevas técnicas, en su mayoría en clínicas privadas.
Subject(s)
Humans , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/therapy , Chile/epidemiology , Molecular Biology , National Health Programs , Acquired Immunodeficiency Syndrome/epidemiology , Tuberculosis Vaccines , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis/mortality , Tuberculosis/prevention & control , Tuberculosis/drug therapyABSTRACT
From the time sarcoidosis has been described, there has always been a viewpoint that the disease is in some way related to tuberculosis (TB). Sarcoidosis is a granulomatous disease, which is likely a result of continued presentation of a poorly degradable antigen. Mycobacterium tuberculosis has been a very strong contender for this antigen. Besides the molecular studies demonstrating mycobacterial deoxyribonucleic acid (DNA) in the sarcoid tissue, assessment of immune responses against mycobacterial antigens provides a useful tool to study the role of mycobacteria in the pathogenesis of sarcoidosis. We reviewed the studies focussing on T-cell and B-cell responses to tubercular antigens in patients with sarcoidosis. Pooled data from various studies does provide a suggestive, though not unequivocal evidence in favour of mycobacteria as a cause of sarcoidosis. These findings not only reinforce the possible pathogenic role of mycobacterial antigens in sarcoidosis, but at the same time also limit the clinical utility of molecular and serological studies based on mycobacterial antigens in the differential diagnosis of TB from sarcoidosis, particularly in a country with high endemicity for TB.