Optimisation of the tuberculin skin test for detection of Mycobacterium bovis in African buffaloes (Syncerus caffer).

Effective screening methods are critical for preventing the spread of bovine tuberculosis (bTB) among livestock and wildlife species. The tuberculin skin test (TST) remains the primary test for bTB globally, although performance is suboptimal. African buffaloes (Syncerus caffer) are a maintenance host of Mycobacterium bovis in South Africa, tested using the single intradermal tuberculin test (SITT) or comparative test (SICTT). The interpretation of these tests has been based on cattle thresholds due to the lack of species-specific cut-off values for African buffaloes. Therefore, the aims of this study were to calculate buffalo-specific thresholds for different TST criteria (SITT, SICTT, and SICTT72h that calculates the differential change at 72 h only) and compare performance using these cut-off values. The results confirm that 3 mm best discriminates M. bovis-infected from unexposed control buffaloes with sensitivities of 69 % (95 % CI 60-78; SITT and SICTT) and 76 % (95 % CI 65-83; SICTT72h), and specificities of 86 % (95 % CI 80-90; SITT), 96 % (95 % CI 92-98; SICTT72h) and 97 % (95 % CI 93-99; SICTT), respectively. A comparison between TST criteria using buffalo-specific thresholds demonstrates that the comparative TST performs better than the SITT, although sensitivity remains suboptimal. Therefore, further research and the addition of ancillary tests, such as cytokine release assays, are necessary to improve M. bovis detection in African buffaloes.

Accuracy of tuberculosis diagnostic tests in small ruminants: A systematic review and meta-analysis.

Tuberculosis (TB) in small ruminants is a neglected disease despite its major impact on goat and sheep production and the global public health. The awareness of the role of small ruminants in the epidemiology of animal TB has increased in the last two decades, however, there is a lack of standardization of procedures and robust quantitative estimates on the accuracy of diagnostic TB tests in the scientific literature. To address this knowledge gap, all the available information regarding the use of ante-mortem diagnostic techniques in small ruminants was collected and summarized through a systematic review process. Furthermore, a random-effects meta-analysis was conducted to separately estimate the sensitivity (Se) and specificity (Sp) of cell-based tests among the retrieved studies in goats. Studies included in the meta-analysis were also evaluated using the Quality Assessment of Diagnostic Accuracy Studies included in systematic reviews adapted for animal diagnostic tests (VETQUADAS). Median pooled Se estimates of the single intradermal tuberculin (SIT) test (ranged from 0.51 to 0.59), the comparative intradermal tuberculin (CIT) test (ranged from 0.30 to 0.50) and the interferon-gamma (IFN-γ) release assay (IGRA) (ranged from 0.66 to 0.72) were lower than that reported previously in cattle, regardless the interpretation criteria and the reporting of MAP infection or vaccination. However, the specificity was adequate for all the tests (ranged from 0.95 to 0.99), except for the SIT test in MAP vaccinated herds (ranged from 0.78 to 0.90). This study provides an overview of the accuracy of diagnostic tests for TB in goats, however, the considerable between-study heterogeneity found hampered the conclusive interpretation of the pooled Se and Sp estimates. Therefore, further studies in small ruminants are necessary to optimize the diagnostic Se, which could help to design effective control strategies, accelerate the eradication of TB in these species and harmonize test procedures.

Skin test of tuberculin purified protein derivatives with a dissolving microneedle-array patch.

BACKGROUND: The tuberculin skin test (TST) is a long-established screening method for tuberculosis. However, the Mantoux technique is often difficult to reliably perform, which affects testing results and safety, which causes local skin pain and pruritus. METHODS: In this study, dissolving microneedle-array patches (MNP) were used to deliver purified protein derivative (PPD) tuberculin into the skin. The skin reaction was compared between MNP delivery and conventional injection. RESULTS: The MNP penetrated the skin easily with a thumb press, and the microneedle dissolved into the skin completely after 1 h. The storage life of MNP loaded with PPD (MNP-PPD) was 7 weeks at atmospheric pressure and room temperature. Only 1/50 dosage of PPD (approximately 0.04 IU) was needed in MNP compared with conventional injection (2 IU) in terms of skin reactivity to TST. When TST was tested in volunteers, the redness and induration of the skin were 19.7 ± 5.6 mm in TB patients, 12.6 ± 4.4 mm in LTBI (latent TB infection) patients, and 5.8 ± 2.7 mm in BCG vaccination healthy volunteers and lasted approximately 26 ± 5.4 days. When applied with MNP-PPD, the redness and induration on the skin decreased significantly to 3.1 ± 0.7 mm in TB patients and 2.0 ± 0.5 mm in LTBI, and the duration time was only 8.5 ± 1.5 days. Moreover, despite the relatively mild skin reactivity in BCG vaccination healthy volunteers with conventional injection, there was no skin reactivity in BCG vaccination healthy volunteers with MNP-PPD. CONCLUSION: In addition to being minimally invasive, needle-free, and painless, no adverse effects were attributed to the new diagnostic method, which may be of value for the safe and effective clinical administration of TB screening. When applied with MNP-PPD, an area of redness and induration greater than 2.5 mm can identify a TB-positive patient.

Evaluation of the McLintock syringe as a cause of non-specific reactions in the intradermal tuberculin test used for the diagnosis of bovine tuberculosis.

The objective of this study was to elucidate whether the use of the McLintock syringe, used to inject tuberculin in cattle in several countries and based on an intradermal inoculation by needle, may, in itself, cause skin reactions that can be interpreted as positive reactions regardless of the real tuberculosis (TB) infection status of the animals. Forty-four cattle from an officially TB-free (OTF) herd were selected for the experiment. Each animal received four inoculations [one with sterile phosphate buffer saline (PBS) with 10% of glycerol and three with bovine purified protein derivative (PPD), as performed during the single intradermal tuberculin (SIT) test], two on each side of the neck (n = 176 inoculations). Three different McLintock syringes (n = 132 inoculations, PBS and bovine PPD) and one Dermojet syringe (n = 44 inoculations, PBS) were used to carry out the inoculations. No positive reactions (increase in skin-fold thickness > 3 mm) in response to the bovine PPD or PBS inoculations were observed regardless of the syringe used. No significant differences (p > 0.05) in the skin fold thickness increase (in mm) were observed between inoculation sites. Significant differences (p < 0.05) in the skin fold thickness were observed when PPD was injected in comparison to the PBS but no differences between McLintock and Dermojet were detected when PBS was injected. The McLintock syringe did not cause reactions per se that could be misunderstood as positive in TB-free cattle demonstrating that it is not a significant factor associated with the previously reported imperfect specificity of the SIT test.

Evaluation of the use of a needle-free injection syringe as a cause of non-specific reactions in the intradermal tuberculin test used for the diagnosis of bovine tuberculosis.

The objective of the study was to elucidate whether the use of the needle-free Dermojet syringe, which is based on a high pressure inoculation and is used to inject tuberculin in cattle in several countries, may, in itself, cause skin reactions that can be interpreted as positive reactions to the intradermal tests that are not, in fact, related to the real infection status of the animals. Forty-four cattle from an officially tuberculosis-free (OTF) herd were selected, and four single intradermal tuberculin (SIT) tests were performed on each animal, two on each side of the neck. Three different Dermojet (D1, D2 and D3) and one McLintock (M4) syringes were used to carry out sterile phosphate buffer saline (PBS) with 10% of glycerol and bovine PPD injections. No positive reactions to the SIT test were observed when using the D1-D3 syringes in the case of either bovine PPD or PBS. With regard to M4 (PBS), all the tests were negative when using a standard interpretation but three were positive in the case of the severe interpretation. Significant differences (p < 0.05) in the skin fold thickness measured were found only between certain Dermojet and McLintock syringes at certain inoculation sites. The results showed that the needle-free Dermojet syringe used for PPD intradermal testing in cattle did not cause significant reactions that could be misunderstood as positives.

Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis.

BACKGROUND: Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. METHODS: All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7. RESULTS: A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75-98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95% CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively. CONCLUSION: The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

Centrifugal Lithography: Self-Shaping of Polymer Microstructures Encapsulating Biopharmaceutics by Centrifuging Polymer Drops.

Polymeric microstructures encapsulating biopharmaceutics must be fabricated in a controlled environment to preserve the biological activity. There is increasing demand for simple methods designed to preserve the biological activity by utilizing the natural properties of polymers. Here, the paper shows that centrifugal lithography (CL) can be used for the fabrication of such microstructures in a single centrifugation, by engineering the self-shaping properties of hyaluronic acid (HA). In this method, HA drops are self-shaped into hourglass-microstructures to produce two dissolving microneedles (DMN), which facilitate transdermal delivery via implantation on the skin. In addition, tuberculin purified protein derivatives are encapsulated into HA DMNs under refrigerated conditions (4 °C) during CL. Therefore, the tuberculin skin test (TST) with the DMNs indicates minimal damage, as opposed to the case of TST with traditional hypodermic needles. These findings on the fabrication of polymeric microstructures with biopharmaceutics may trigger the development of various biomedical devices and therapies.

The QuantiFERON-TB Gold In-Tube Assay in Neuro-Ophthalmology.

BACKGROUND: Although QuantiFERON-TB Gold In-Tube (QFT-GIT) testing is regularly used to detect infection with Mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (TB) has been questioned. The following is a cohort study analyzing the efficacy of QFT-GIT testing as a method for detection of active TB disease in low-risk individuals in a neuro-ophthalmologic setting. METHODS: Ninety-nine patients from 2 neuro-ophthalmology centers were identified as having undergone QFT-GIT testing between January 2012 and February 2016. Patients were divided into groups of negative, indeterminate, and positive QFT-GIT results. Records of patients with positive QFT-GIT results were reviewed for development of latent or active TB, as determined by clinical, bacteriologic, and/or radiographic evidence. RESULTS: Of the 99 cases reviewed, 18 patients had positive QFT-GIT tests. Of these 18 cases, 12 had documentation of chest radiographs or computed tomography which showed no evidence for either active TB or pulmonary latent TB infection (LTBI). Four had chest imaging which was indicative of possible LTBI. None of these 18 patients had symptoms of active TB and none developed active TB within the follow-up period. CONCLUSIONS: Based on our results, we conclude that routine testing with QFT-GIT in a low-risk cohort did not diagnose active TB infection. We do not recommend routine QFT-GIT testing for TB low-risk individuals, as discerned through patient and exposure history, ocular examination, and clinical judgment, in neuro-ophthalmology practice.

[COMPARISON OF QuantiFERON® TB GOLD TEST RESULTS BEFORE AND AFTER ENDOTOXIN CONTAMINATION].

PURPOSE: In response to a case of endotoxin contamination of tubes used in QuantiFERON® TB Gold (QFT-3G) testing in Japan in 2013, the effect of this contamination on QFT-3G test results was investigated. METHODS: We analyzed QFT-3G results from 4,258 participants in a tuberculosis contact investigation in Yamagata, Japan from September 2010 to April 2015. Of these, 2,488 samples were collected before the endotoxin contamination, while 1,770 samples were collected after the contamination. RESULTS: Negative control values in the group tested after the contamination were significantly lower than those in the group tested before the contamination (P < 0.0005). The proportion of positive controls that exceeded the calculated limit (10IU/ml) in the group tested after the contamination (87.8%) was lower than that in the group tested before the contamination (96.8%; P < 0.0005). The proportion of intermediate results in the group tested after the contamination (3.2%) was markedly lower than that in the group tested before the contamination (6.6%). DISCUSSION: Differences in QFT-3G test results were found to be related to a difference in blood collection before or after endotoxin contamination of blood collection tubes. Values resulting from QFT-3G testing were lower in blood samples that were collected after the contamination relative to those collected before the contamination.

Safety and efficacy of tuberculin skin testing with microneedle MicronJet600™ in healthy adults.

SETTING: Intradermal injection using a syringe and needle is generally accepted as the most accurate method for the tuberculin skin test (TST). However, the Mantoux technique using a conventional needle is often difficult to perform reliably, affecting testing results and safety. OBJECTIVE: We evaluated the efficacy and safety of a novel intradermal injection device, the MicronJet600(TM) microneedle, compared with conventional injection in terms of skin reactivity to the TST. DESIGN: A prospective, open-label clinical study was conducted. The TST was administered by both methods in the same subject. For pain assessment, participants filled in a visual analogue scale (VAS) after each TST. Any side effects due to TST or injections were observed. RESULTS: TST reaction rates (cut-off ⩾5 mm) from microneedles and needles were respectively 44.0% and 47.2%, with no significant difference between the two. Furthermore, agreement of positivity between the two methods was excellent with both 5 mm and 10 mm cut-off values. However, the level of pain experienced when microneedles were used for TST was significantly lower than with conventional needles. No adverse effects were attributed to the MicronJet device. CONCLUSION: The novel microneedle device used for TST in this study was effective, safe and less painful in healthy adult volunteers.

Utility of QuantiFERON-TB Gold In-Tube Test in the Diagnosis of Latent TB in HIV-Positive Patients in a Medium-TB Burden Country.

BACKGROUND: The authors aimed to compare TST with QuantiFERON-TB Gold In-Tube (QFT) for detecting latent tuberculosis infection (LTBI) in HIV-infected patients in Iran as a TB-medium endemic country. METHODS: In a cross-sectional design,130 HIV-positive patients in HIV clinic of Tehran University were studied. Patients screened for LTBI with QFT and TST simultaneously. Concordance between 2 tests results and variables associated with tests discordance were assessed. RESULTS: Positive results found in 24.6% for TST and 7.7% for QFT. Overall agreement between them was 73.85% (Kappa = 0.083). History of imprisonment was associated with more positive TST (P = 0.014) and QFT (P = 0.01). Patients with intravenous drug use (IDU) history had significant discordant results (0.018). CONCLUSION: The authors recommend QFT for all negative cases of TST in HIV-positive patients especially who had history of IDU.

Conversión de tuberculina en trabajadores del Hospital Universitario San Ignacio y asociación con características demográficas y laborales / Tuberculin skin test conversion and association with occupation and demographic characteristics in workers at San Ignacio University Hospital

Objetivos: Establecer la prevalencia de positividad, la tasa de conversión de la tuberculina en trabajadores de nuestro hospital y describir las características demográficas y laborales asociadas a esto. Materiales y Métodos Estudio observacional descriptivo en una cohorte de trabajadores del hospital a los que se les realizó la prueba de tuberculina. Se definió la positividad de la prueba de tuberculina como un resultado mayor o igual a 10 mm y la conversión como un aumento de 6 o 10 mm con respecto a la prueba inicial. Resultados Se encontró una prevalencia de 23,7 % y una incidencia de conversión de 13,6 % para el punto de corte mayor de 10 mm y 23 % para el punto de corte de 6 mm. La edad de los sujetos estuvo relacionada a conversión, mientras que no se encontró relación con la ocupación. Conclusión La probabilidad de transmisión de la tuberculosis en trabajadores del hospital es mayor al de la población general. Deben ser implementadas medidas de promoción y prevención para disminuir la transmisión e incrementar el conocimiento de la tuberculosis asociada al cuidado de la salud en los trabajadores.(AU)

Objectives To establish the prevalence of positivity and conversion rate of the tuberculin skin test in workers of our hospital, and to describe the related demographic and occupational characteristics. Materials and Methods An observational, descriptive study was conducted in a cohort of hospital workers who underwent the tuberculin skin test. The positivity of the test was defined as a result of greater than or equal to 10 mm, and conversion was defined as an increase of 6 or 10 mm with respect to the initial test. Results Prevalence of 23.7 % and incidence of conversion of 13.6 % for the major cut-off point of 10 mm, and 23 % for the lesser cut-off point of 6 mm, was found. The age of the subjects was related to the conversion, but there was no relation with occupation. Conclusions The probability of tuberculosis transmission in health-care workers is higher than in the general population. Promotion and prevention measures must be implemented to decrease the transmission and to increase awareness of tuberculosis related to occupational activities.(AU)

Diagnosis of latent tuberculosis in patients with systemic lupus erythematosus: T.SPOT.TB versus tuberculin skin test.

UNLABELLED: Early studies in patients with systemic lupus erythematosus (SLE) reported increased incidence of tuberculosis. The tuberculin skin test (TST) is the technique of choice to detect latent tuberculosis infection (LTBI) but has several limitations. OBJECTIVES: We compared TST and the newer T.SPOT.TB test to diagnose LTBI in SLE patients. METHODS: In this observational cohort study conducted between August 2009 and February 2012, we recruited 92 patients from those attending the SLE clinic of our university hospital. Data recorded were epidemiological and sociodemographic characteristics. Laboratory analyses included TST and T.SPOT.TB tests. RESULTS: Of the patients studied, 92% were women with an average age of 42.7 years. Overall, the degree of correlation between the two tests was low (Kappa index = 0.324) but was better in patients not receiving corticosteroids (CTC)/immunosuppressive (IS) therapy (Kappa = 0.436) and in those receiving hydroxychloroquine (Kappa = 0.473). While TST results were adversely affected by those receiving CTC and/or IS drugs (P = 0.021), the T.SPOT.TB results were not. CONCLUSION: Although the TST test remains a useful tool for diagnosing LTBI in SLE patients, the T.SPOT.TB test is perhaps better employed when the patient is receiving CTC and/or IS drugs.

Chitin microneedles for an easy-to-use tuberculosis skin test.

An easy-to-use tuberculosis skin test is developed with chitin microneedles that deliver purified protein derivative at the correct skin depth and result in a positive test in BCG-immunized guinea pigs.

Comparison of different methods and times for reading the tuberculin skin test.

BACKGROUND: Current guidelines vary on the recommended method and time for measuring tuberculin skin test (TST) indurations. OBJECTIVE: To evaluate the best time and method for assessing TST results and which purified protein derivative (PPD) to administer. DESIGN: Standard PPD (PPD-S) and PPD-RT23 were applied concurrently on each forearm in random order in 78 nurses. MEASUREMENTS: TST induration was measured at 48, 72 and 96 h by two nurses by palpation and a ruler, palpation and a Vernier caliper, ballpoint pen and a ruler or ballpoint pen and a Vernier caliper. TST differences were assessed using mixed-effects analysis. We also assessed the rate of false-positive/-negative results and the variability of the TST measurements. RESULTS: We performed 767 TST measurements. The adjusted mean TST size was larger with PPD-S than with PPD-RT23 (12.8 vs. 10.8 mm, P < 0.001), and at 72 h than at 48 h and 96 h (13.4 vs. 11.8 vs. 10.1 mm, P < 0.05). The smallest number of false results was observed with PPD-S, the ballpoint pen-ruler and at 72 h; palpation+ruler had the least variability at 72 h. CONCLUSIONS: The TST should ideally be performed with PPD-S and measured at 72 h with the ballpoint pen+ruler or palpation+ruler methods.

Serial testing of Malaysian health care workers with QuantiFERON®-TB Gold In-Tube.

BACKGROUND: Serial testing for tuberculosis (TB) exposure has been advocated among health care workers (HCWs) at risk of nosocomial infection. OBJECTIVE: To determine the incidence and factors associated with TB infection among selected HCWs in Malaysia and to determine interferon-gamma response in serial testing. DESIGN: A cohort of 769 HCWs were retested after 1 year using QuantiFERON®-TB Gold In-Tube. Incidence of TB infection was determined among HCWs who previously tested negative. Conversion and reversion rates using several definitions were explored. RESULTS: Incidence of TB infection was 9.9 per 100 workers per year (95%CI 7.9-12.3). Working in the Emergency Department (ED; RR 2.18, 95%CI 1.07-4.43) was significantly associated with risk of TB infection. Reversion and conversion occurred frequently, with 46.7% reversion among HCWs with baseline interferon-gamma (IFN-γ) levels of 0.35-0.70 international units (IU)/ml, and 23.8% conversion among HCWs with baseline IFN-γ levels of 0.20-0.34 IU/ml. CONCLUSIONS: TB infection control measures need to be strengthened, particularly in the ED, as the incidence of TB was high. Conversion and reversion rates in serial testing were high, and further studies are needed to facilitate its interpretation.

Retrospective return on investment analysis of an electronic treatment adherence device piloted in the Northern Cape Province.

OBJECTIVE: The return on investment (ROI) for utilizing the SIMpill electronic treatment adherence solution as an adjunct to directly observed treatment short-course (DOTS) is assessed using data from a 2005 pilot of the SIMpill solution among new smear-positive tuberculosis (TB) patients in the Northern Cape Province. The value of this cost minimization analysis (CMA), for use by public health planners in low-resource settings as a precursor to more rigorous assessment, is discussed. MATERIALS AND METHODS: The retrospective analysis compares the costs and health outcomes of the DOTS-SIMpill cohort with DOTS-only controls. Hypothetical 5-year cash flows are generated and discounted to estimate net present values (NPVs). RESULTS: Comparison between the DOTS-SIMpill pilot cohort and DOTS-only supported controls, for a hypothetical implementation of 1,000 devices, over 5 years, demonstrates positive ROI for the DOTS-SIMpill cohort based on improved health outcomes and reduced average cost per patient. The net stream is shown to be positive from the first year. Discounted NPV is ZAR 3,255,256 (US$ 493,221) for a cohort that would have started mid 2005 and ZAR 3,747,636 (US$ 487,339) starting mid 2010. This is an ROI of 23% over the 5-year period. CONCLUSION: The addition of electronic treatment adherence support technology can help to improve TB outcomes and lower average cost per patient by reducing treatment failure and the associated higher cost and burden on limited resources. CMA is an appropriate initial analysis for health planners to highlight options that may justify more sophisticated methods such as cost effectiveness analysis or full cost benefit analysis where a preferred option is immediately revealed. CMA is proposed as a tool for use by public health planners in low-resource settings to evaluate the ROI of treatment adherence technology postpilot and prior to implementation.

Teste tuberculínico: comparação de dois instrumentos de leitura / Tuberculin skin test comparison of two reading instruments

Introdução- A busca ativa de indivíduos infectados pelo Mycobacterium tuberculosis, com o auxílio do teste tuberculínico, principalmente em populações de detentos, moradores de rua, infectados pelo vírus do HIV entre outras, tem como objetivo prevenir a evolução da infecção para a doença tuberculose e auxiliar o conhecimento de novos casos da doença. O teste tuberculínico é uma importante ferramenta, para identificar os indivíduos reatores (infectados) e não reatores (não infectados). Ele pode ser aplicado a partir de várias técnicas, mas a que permite a padronização e a comparação dos resultados é a técnica intradérmica de Mantoux, a mais usada atualmente. No Brasil, a leitura do resultado do teste tuberculínico é realizada, por recomendação do Ministério de Saúde, com régua milimetrada. Para seu uso é necessário um treinamento rigoroso, o que tem contribuído para a diminuição de leitores do teste tuberculínico na rotina dos serviços de saúde. Como alternativa temos outro instrumento, paquímetro, ainda não padronizado no Brasil. Outros países o utilizam nas rotinas dos serviços de saúde para busca de indivíduos reatores ou não ao teste tuberculínico, ele não cabe para aferição ou inquéritos epidemiológicos. Objetivo- Comparar os instrumentos de leitura dos resultados do teste tuberculínico obtidos através da leitura padronizada, feita por régua milimetrada, e a leitura, não padronizada, feita por paquímetro. Métodos- Estudo descritivo realizado numa população prisional de uma Penitenciária e de um Centro de Detenção Provisória, da cidade de Guarulhos, Grande São Paulo, entre os meses de março a junho de 2008. Foi realizada a leitura do teste tuberculínico de forma dupla cega, por dois leitores, com instrumentos diferentes, paquímetro e régua milimetrada. Resultados- Foram administrados testes tuberculínicos em 1954 indivíduos; destes 111 foram excluídos por não terem comparecido à leitura do teste, resultando em uma amostra de 1843 indivíduos divididos em 1059 (57,5 por cento ) na Penitenciária e 784 (42,5 por cento ) no Centro de Detenção Provisória. Os resultados comparativos entre os dois instrumentos, quando avaliados os reatores com os não reatores, foram altos e equivalentes, pois a sensibilidade (93 por cento ) e a especificidade (97 por cento ) foram praticamente as mesmas. A média da concordância foi alta entre os dois instrumentos (95,5 por cento ) e a discordância foi baixa (4,5 por cento ).

Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection.

BACKGROUND: During screening for latent tuberculosis infection (LTBI), before anti-tumor-necrosis-factor-α treatment, most patients are already receiving immunosuppressive therapy. The objective was to evaluate the performance of the QuantiFERON Gold In-Tube (QFT-IT) and the Tuberculin Skin Test (TST). METHODS: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44). RESULTS: QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had ≥1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone treatment interferon gamma (IFN-γ) response to mitogen stimulation was impaired (median IFN-γ response 4.9 IU/mL; interquartile range [IQR] 0.8 to ≥10.0) compared to patients 1) not receiving corticosteroids (median ≥10.0; IQR 5.0 to ≥10.0; P = 0.0015) or 2) receiving long-acting corticosteroids (median >10.0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P < 0.001), whereas no negative effect was found for long-acting corticosteroids. Doses of ≥10 mg prednisolone were associated with a 27% risk of indeterminate results. Single use of azathioprine, methotrexate, or 5-aminosalicylate (5-ASA) did not affect the test results. CONCLUSIONS: Oral prednisolone severely suppressed QFT-IT and TST performance, whereas the long-acting corticosteroids methotrexate, azathioprine, and 5-ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT-IT or TST prior to initiation of prednisolone therapy and negative QFT-IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available.

Factors influencing the performance of an interferon-γ assay for the diagnosis of tuberculosis in goats.

The interferon-gamma (IFN-γ) assay is an effective tool for the diagnosis of tuberculosis (Tb) in goats. The objectives of this study were to evaluate factors that might affect assay performance: (1) the phenol concentration of the purified protein derivative (PPD, tuberculin) used; (2) dialysis of PPD; and (3) delaying antigenic stimulation of blood samples for 8, 16 and 24h after collection. The assay was performed in duplicate with two cut-off points. Dialysis of PPD reduced test sensitivity, whereas the concentration of phenol did not significantly affect test outcome. Delaying antigenic stimulation of samples >8h resulted in a reduction in test sensitivity, compromising the capacity of the assay to detect infected animals. Performing the assay in duplicate was unnecessary, which has implications for reducing assay costs. These findings will facilitate the effective application of the IFN-γ assay as an ancillary test in Tb eradication programmes in goats.