Comparison of two interferon gamma release assays in the diagnosis of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> infection and disease in The Gambia

Background  

IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Their performance may depend on assay format and may vary across populations and settings. We compared the diagnostic performance of an in-house T -cell and commercial whole blood-based IGRAs for the diagnosis of LTBI and TB disease in The Gambia.     

Latent tuberculosis among pregnant mothers in a resource poor setting in Northern Tanzania: a cross-sectional study

Background  

Untreated latent TB infection (LTBI) is a significant risk factor for active pulmonary tuberculosis, hence predisposing to adverse pregnancy outcomes and mother to child transmission. The prevalence of latent tuberculosis in pregnancy and its association, if any, with various socio-demographic, obstetric and clinical characteristics was evaluated.     

Effectiveness of the combination of a whole‐blood interferon‐gamma assay and the tuberculin skin test in detecting latent tuberculosis infection in rheumatoid arthritis patients receiving adalimumab therapy

Objective

To investigate QuantiFERON‐tuberculosis Gold (QFT‐G) assay and tuberculin skin test (TST) for latent tuberculosis (TB) infection (LTBI) in patients with rheumatoid arthritis (RA) treated with adalimumab.

Methods

We prospectively followed up 43 RA patients who received adalimumab therapy and underwent serial TSTs and QFT‐G assays. TST was performed using Mantoux method and QFT‐G assay was examined by measuring interferon‐γ levels in whole blood samples that were incubated with early secretary antigenic target‐6 and culture filtrate protein 10.

Results

Before starting adalimumab therapy, 8 RA patients (18.6%) had positive and 35 (81.4%) had negative TST results. All 8 RA patients with positive TST results were diagnosed as LTBI and received isoniazid prophylaxis (INHP) 1 month before starting adalimumab therapy. None of these 8 RA patients developed active TB 2 years after completing INHP. A high rate (10 [37.0%] patients) of TST conversion was observed among 27 patients who had completed 12‐month adalimumab therapy. Of these 10 patients with TST conversion, 2 patients had positive QFT‐G results and 1 developed active TB disease. Among 17 RA patients who did not have TST conversion after 12‐month adalimumab therapy, 1 patient who had a positive QFT‐G result developed active TB disease. Of all 43 RA patients who received adalimumab therapy, 4 (9.3%) developed active TB after starting adalimumab therapy.

Conclusion

The application of TST for detecting LTBI is limited in RA patients by the frequent presence of anergy. Combined QFT‐G assay and TST can aid in detecting LTBI in RA patients receiving adalimumab therapy.     

Infection control and the burden of tuberculosis infection and disease in health care workers in china: a cross-sectional study

Background  

Hospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China.     

Tuberculosis,focussed tools and the right schools: estimated impact and cost of a targeted student screening programme for tuberculosis infection

Background

The World Health Organization (WHO) recommends targeted screening for latent tuberculosis infection (LTBI) among high-risk populations. Recent studies that evaluate targeted school-based programmes in low burden settings are scarce.

Aims

To evaluate a school screening programme for recently arrived migrant students from moderate and high tuberculosis (TB) burden countries and estimate (1) the number of cases of active TB that were prevented and (2) the cost per case of active TB prevented.

Methods

Students were screened with tuberculin skin tests (TST) at schools with a high migrant population intake. Those with positive results were referred for specialist evaluation. Outcomes were retrospectively assessed using 5 years of prospectively collected data. Cost data were collected. Main outcomes measured were the number of children were diagnosed with LTBI who completed treatment, and programme costs.

Results

Of 4728 student screened, 295 (6.2%) were diagnosed with LTBI. Of these, 273 (92.5%) were offered preventive therapy, 242 (82.0%) commenced and 204 (69.2%) completed therapy. The number needed to screen (NNS) was 23 per completed course of preventive treatment for LTBI. Assuming a 10% lifetime risk of reactivation, the NNS was 386 per case of TB disease notification avoided. The cost of screening was A$23 932 per case of TB disease avoided.

Conclusions

This TB strategy is supported by the high rate of TB infection in the student group, the treatment uptake and completion rates. Cost–benefit is linked with lifetime risk of TB reactivation. Targeted school screening programmes represent an important opportunity for TB control in low-burden settings.     

Risk of latent TB infection in individuals employed in the healthcare sector in Germany: a multicentre prevalence study

Background  

Healthcare workers are still recognised as a high-risk group for latent TB infection (LTBI). Therefore, the screening of people employed in the healthcare sector for active and LTBI is fundamental to infection control programmes in German hospitals. It was the aim of the study to determine the prevalence and putative risk factors of LTBI.     

Humoral response to HspX and GlcB to previous and recent infection by <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis>

Background  

Tuberculosis (TB) remains a major world health problem. Around 2 billions of people are infected by Mycobacterium tuberculosis, the causal agent of this disease. This fact accounts for a third of the total world population and it is expected that 9 million people will become infected each year. Only approximately 10% of the infected people will develop disease. However, health care workers (HCW) are continually exposed to the bacilli at endemic sites presenting increased chance of becoming sick. The objective of this work was to identify LTBI (latent tuberculosis infection) among all asymptomatic HCW of a Brazilian Central Hospital, in a three year follow up, and evaluate the humoral response among HCW with previous and recent LTBI to recombinant HspX and GlcB from M. tuberculosis.     

Community-based cross-sectional survey of latent tuberculosis infection in Afar pastoralists,Ethiopia, using QuantiFERON-TB Gold In-Tube and tuberculin skin test

Background  

There is little information concerning community-based prevalence of latent tuberculosis infection (LTBI) using T-cell based interferon-γ (IFN-γ) release assays (IGRAs), particularly in TB endemic settings. In this study, the prevalence of LTBI in the Afar pastoral community was assessed using QuantiFERON-TB Gold In-Tube (QFTGIT) and tuberculin skin tests (TST).     

Sex- and age-dependent association of <Emphasis Type="Italic">SLC11A1</Emphasis>polymorphisms with tuberculosis in Chinese: a case control study

Background  

Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB.     

Post-treatment change in Mycobacterium tuberculosis antigen-stimulated tumor necrosis factor-alpha release in patients with active tuberculosis

Background

Monitoring tuberculosis (TB) treatment response remains challenging due to lack of reliable laboratory markers. In recent years, increased efforts have been exerted toward development of new biomarkers reflecting treatment response appropriately. While performance of interferon-gamma release assays (IGRAs) to monitor anti-TB treatment has been extensively evaluated, there is no data about post-treatment changes in Mycobacterium tuberculosis (MTB) antigen-stimulated tumor necrosis factor-alpha (TNF-α) release in active TB patients. Herein, we explored whether the MTB antigen-stimulated TNF-α release would be useful for monitoring responses to anti-TB treatment.

Methods

We compared unstimulated (TNF-α_Nil), MTB antigen-stimulated (TNF-α_Ag), and MTB antigen-stimulated minus unstimulated TNF-α levels (TNF-α_Ag-Nil) in supernatants from QuantiFERON-TB Gold In-Tube tests before and after treatment in 16 active TB patients, 25 latent TB infection (LTBI) subjects, and 10 healthy controls (HC).

Results

TNF-α_Ag and TNF-α_Ag-Nil levels decreased significantly after treatment in patients with active TB. In addition, TNF-α_Nil, TNF-α_Ag, and TNF-α_Ag-Nil levels were significantly higher in untreated active TB patients compared to LTBI subjects and HC.

Conclusions

This finding cautiously suggests that MTB Ag-stimulated TNF-α response may be a potential adjunctive marker for monitoring treatment response in active TB patients.     

Application and interpretation of an interferon-gamma release assay: Results of an audit in a Canadian centre

BACKGROUND:

Interferon-gamma release assays (IGRAs) are newly approved for diagnosing latent tuberculosis infection (LTBI). An internal audit was conducted to review the use of a newly implemented IGRA at the Hôpital du Sacré-Coeur de Montréal (Montréal, Québec) to evaluate its concordance with Canadian recommendations and its implication on diagnosis.

METHODS:

From April 2007 to January 2009, all Quantiferon TB Gold In-Tube (QFT, Cellestis inc, USA) tests performed in at the Hôpital du Sacré-Coeur de Montréal were retrieved. Strategies used to investigate LTBI and clinical interpretation of test results were compared with the local algorithm, which is derived from the current national guidelines.

RESULTS:

A total of 200 patients tested with QFT were included in the analysis. LTBI investigation and QFT testing were considered to be appropriate in 87.5% and 66.5% of patients, respectively. Overall, 67 QFT tests were performed inappropriately; 25 were performed when a LTBI investigation was not indicated and 42 were performed whe LTBI interpretation was possible with the result of the tuberculin skin test alone. Among the 175 patients investigated appropriately for LTBI, 49 QFT tests (28%) were interpreted incorrectly; 32 patients (at high risk of developing active tuberculosis) had a positive tuberculin skin test and a negative QFT result wrongly interpreted as being negative for LTBI and 13 patients should have undergone further LTBI investigations.

CONCLUSION:

Globally, the present study revealed that there are discrepancies on how the IGRA was employed and interpreted in a Montreal hospital and that strict compliance to the guidelines could significantly reduce errors in interpretation.     

Tuberculin skin test and interferon-γ release assays: Can they agree?

Introduction

The diagnosis of latent tuberculosis infection (LTBI) relies largely on the tuberculin skin test (TST) or, more recently, on interferon-gamma release assays (IGRA). Knowledge regarding these tests is essential to improve their usefulness in combating the tuberculosis epidemic.

Objectives

To characterize the agreement between the IGRA and TST tests by determining the kappa coefficient (K) and agreement rate between these two tests in patients with active tuberculosis (TB).

Methods

Retrospective cohort study conducted with data from active TB patients notified in the Portuguese Tuberculosis Surveillance System (SVIG-TB), from 2008 to 2015. TST results were interpreted using a 5 mm (TST-5 mm) and 10 mm (TST-10 mm) cutoff. Kappa coefficient and agreement rate were calculated in order to evaluate the agreement between IGRA and TST (both cutoffs) test results.

Results

A total of 727 patients with results for both tests were included in the study, of which 3.4% (n = 25) had HIV infection, 5.6% (n = 41) diabetes, 5.0% (n = 36) oncological diseases and 4.4% (n = 32) inflammatory diseases. Of the 727 patients, 16.5% (n = 120) presented different outcomes between IGRA and TST-5 mm, and 20.5% (n = 149) presented different outcomes between IGRA and TST-10 mm. Kappa coefficient between IGRA and TST-5 mm was 0.402 (p < 0.001) with an agreement rate of 83.5%. Between IGRA and TST-10 mm, the kappa coefficient was 0.351 (p < 0.001), with an agreement rate of 79.5%. Patients with HIV infection, diabetes, oncologic diseases and inflammatory diseases presented a substantial agreement between IGRA and TST-5 mm, while inflammatory diseases was the only variable that presented a substantial agreement between IGRA and TST-10 mm.

Conclusion

As both tests can present false-negative results, the low level of agreement between the tests can potentially help identify more cases of LTBI if the two tests are used in parallel, with infections not detected by IGRA possibly being detected by the TST and vice versa.     

Diagnosis and follow-up of treatment of latent tuberculosis; the utility of the QuantiFERON-TB Gold In-tube assay in outpatients from a tuberculosis low-endemic country

Background

Interferon-gamma (IFN-γ) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON^®-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.

Methods

481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.

Results

The QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST ≥ 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-γ responses were comparable at start (mean 6.13 IU/ml ± SD 3.99) and after three months (mean 5.65 IU/ml ± SD 3.66) and 15 months (mean 5.65 IU/ml ± SD 4.14), (p > 0.05).

Conclusion

Only one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.

     

Toxicity and adherence to treatment for latent tuberculosis infection in patients with hematologic malignancies

Purpose

Oncohematological patients undergoing chemotherapy who have latent tuberculosis infection (LTBI) are at a high risk of developing active tuberculosis (TB). The identification and treatment of these patients can prevent LTBI progressing to active TB. This study analyzed the degree of adherence with and safety of the treatment of latent tuberculosis infection (TLTBI) in oncohematological patients undergoing antineoplastic chemotherapy.

Methods

This is a retrospective study of a cohort of oncohematological patients receiving TLTBI and antineoplastic chemotherapy simultaneously, between January 2007 and June 2010. The proportions of toxicity and adherence to TLTBI in these patients were compared with a non-oncohematological control group, matched for age, sex, and year in which the TLTBI was started. In addition, a minimum 2-year follow-up was carried out for all patients.

Results

A total of 105 patients who received TLTBI were included, 21 of whom had received antineoplastic chemotherapy simultaneously. The mean age of the patients was 63 years. There were no significant baseline differences in transaminase values. The percentages of patients completing treatment were 76.2 % in the control group and 71.4 % in the oncohematological group [risk ratio (RR): 1.07, 95 % confidence interval (CI): 0.79–1.43]. The voluntary dropout proportion was similar in both groups (12.3 vs. 11.8 %, RR: 1.05, 95 % CI: 0.25–4.42). Treatment was discontinued because of toxicity in three oncohematological patients and in 11 patients from the control group (RR: 1.14; 95 % CI: 035–3.66). No patient developed TB during the follow-up period.

Conclusion

The safety of TLTBI is not influenced by simultaneous antineoplastic chemotherapy in oncohematological patients.     

Screening and follow-up of children exposed to tuberculosis cases, Luanda, Angola

This prospective study enrolled children aged < 5 years with reported contact with adult tuberculosis (TB) patients in Angola. The study sample consisted of 124 children: 70 (56.5%) were active TB cases, 22 (17.7%) had latent TB infection (LTBI) and 32 (25.8%) were TB-exposed; 14 (20%) were human immunodeficiency virus positive. After 6 months of follow-up, 31.8% of the LTBI cases had evolved to active TB and 9.4% of the non-infected children had developed active TB. The strategy of simultaneous chest X-ray and TB skin test used in this study was effective; despite this protocol, however, 31.8% LTBI children developed active TB.     

Prevalence of hepatitis B virus (HBV) and latent tuberculosis co-infection and risk of drug-induced liver injury across two large HBV cohorts in the United States

The epidemiology of latent tuberculosis and hepatitis B virus (HBV-LTBI) co-infection among U.S. populations is not well studied. We aim to evaluate LTBI testing patterns and LTBI prevalence among two large U.S. cohorts of adults with chronic HBV (CHB). Adults with CHB in the Chronic Hepatitis Cohort Study (CHeCS) and Veterans Affairs national cohort were included in the analyses. Prevalence of HBV-LTBI co-infection was defined as the number of HBV patients with LTBI divided by the number of HBV patients in a cohort. Multivariable logistic regression evaluated odds of HBV-LTBI co-infection among CHB patients who underwent TB testing. Among 6019 CHB patients in the CHeCS cohort (44% female, 47% Asian), 9.1% were tested for TB, among whom 7.7% had HBV-LTBI co-infection. Among HBV-LTBI co-infected patient, only 16.7% (n = 7) received LTBI treatment, among whom 28.6% (n = 2) developed DILI. Among 12,928 CHB patients in the VA cohort (94% male, 42% African American, 39% non-Hispanic white), 14.7% were tested for TB, among whom 14.5% had HBV-LTBI. Among HBV-LTBI co-infected patient, 18.6% (n = 51) received LTBI treatment, among whom 3.9% (n = 3) developed DILI. Presence of cirrhosis, race/ethnicity, and country of birth were observed to be associated with odds of HBV-LTBI co-infection among CHB patients who received TB testing. In summary, among two large distinct U.S. cohorts of adults with CHB, testing for LTBI was infrequent despite relatively high prevalence of HBV-LTBI co-infection. Moreover, low rates of LTBI treatment were observed among those with HBV-LTBI co-infection.     

The performance and limitation of T-SPOT.TB for the diagnosis of TB in a high prevalence setting

Background

Tuberculosis (TB) diagnosis remains difficulty. The previous reports have shown that the T-SPOT.TB assay may be a more promising diagnostic tool for TB, however, it needs a further study to evaluate the diagnostic value of T-SPOT.TB for the specific populations in a high prevalence setting.

Methods

In this present study, we conducted stratified and comparable analyses to explore the clinical value and the limitation of T-SPOT.TB assay in TB diagnosis in a high TB prevalence setting, Southern China. A total of 413 subjects including 163 pulmonary TB (PTB), 39 extrapulmonary TB (EPTB), 106 non-TB pulmonary diseases (NTBPDs), 20 medical staff and 85 healthy controls were included in the study.

Results

According to T-SPOT.TB, there had a high incidence of latent TB infection (LTBI) in general population in Southern China, especially in the NTBPDS and medical staff. The T-SPOT.TB had a high performance in the diagnosis of active TB (ATB) in a lower risk of TB infection population such as the general population, however, the T-SPOT.TB for the diagnosis of ATB in the high risk of TB infection populations involving close contacts such as the patients with pulmonary diseases (PD) or medical staff isn’t reliable due to the interference by LTBI. Under this condition, the value of rule-out of the assay was seemed to be better than that of rule-in. We believed that the T-SPOT.TB is suitable for screening both the EPTB and the ATB combined with diabetes mellitus (DM). However, we found that the sensitivity of T-SPOT.TB in sputum smear-negative population wasn’t as high as that in smear-positive population.

Conclusions

The T-SPOT.TB testing results should be interpreted with caution combined with subject’s characteristics in a high prevalence setting.     

Comparison of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> culture using liquid culture medium and Lowenstein Jensen medium in abdominal tuberculosis

Background  

Traditionally, the Lowenstein Jensen (LJ) medium has been used for culturing Mycobacterium tuberculosis. In abdominal tuberculosis (TB), the reported yield from tissue culture is between 20% and 60%. Liquid cultures are reported to give a higher yield but there is little data available in abdominal TB.     

Response to <Emphasis Type="Italic">M. tuberculosis</Emphasis>selected RD1 peptides in Ugandan HIV-infected patients with smear positive pulmonary tuberculosis: a pilot study

Background  

Tuberculosis (TB) is the most frequent co-infection in HIV-infected individuals still presenting diagnostic difficulties particularly in developing countries. Recently an assay based on IFN-gamma response to M. tuberculosis RD1 peptides selected by computational analysis was developed whose presence is detected during active TB disease. Objective of this study was to investigate the response to selected RD1 peptides in HIV-1-infected subjects with or without active TB in a country endemic for TB and to evaluate the change of this response over time.     

<Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis>spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in peri-urban Kampala,Uganda

Background  

The poor peri-urban areas of developing countries with inadequate living conditions and a high prevalence of HIV infection have been implicated in the increase of tuberculosis (TB). Presence of different lineages of Mycobacterium tuberculosis has been described in different parts of the world. This study determined the predominant strain lineages that cause TB in Rubaga division, Kampala, Uganda, and the prevalence of resistance to key anti-tuberculosis drugs in this community.