Contribution of T-SPOT.TB Assay to the Diagnosis of Active Tuberculosis Infection among Chronic Kidney Disease Patients on Immunosuppressive Therapy

This article refers to:

The Application of T.SPOT-TB Assay for Early Diagnosis of Active Tuberculosis in Chronic Kidney Disease Patients Receiving Immunosuppressive Treatment

Tuberculosis (TB), a disease which plagued humanity over the centuries, has initial literary traces in Indian Vedas and Chinese medical texts predating the Xia dynasty some 3500–5700 years ago [1]. Though an ancient disease, little was known about the origins, evolution, and spread of the TB till recently. In 1974, the first ever link between TB and chronic kidney disease (CKD) was reported in a case series [2]. Patients with CKD, a persistent inflammatory state, are at higher risk for TB which is compounded by the poor socioeconomic, comorbid, and other demographic factors. The global prevalence of the CKD is increasing in the parts of the world where the TB is endemic, especially in low- to middle-income countries such as India and China, leading to increased mortality, morbidity, and challenging the respective public health organizations and raising the health-care budgets. Unfortunately, the screening and diagnostic test performances for TB, and related, reliable, coordinated protocols, are lacking for the global CKD population given the lack of substantial evidence on the subject.

The published literature confirmed a 6.9 to 52.5-fold higher risk of TB in CKD patients particularly in those on dialysis than the general population [3]. The screening of the TB in CKD population helps to detect the asymptomatic and minimally symptomatic active TB patients and the ones with LTBI, leading to early detection and treatment which is an essential element of the disease control. The tuberculin (purified protein derivative-PPD) skin test (TST) has been used as an in vivo test to detect LTBI for well over 50 years and has longitudinal data which provide the predictive information. TST lacks the specificity, as the preparation contains antigens which cross-react with BCG and other non-tuberculous mycobacteria [4] and is less sensitive in immunosuppressed patients. The interferon-γ release assays (IGRAs) such as the T-SPOT.TB test (Oxford Immunotec Limited, Abingdon, UK) and the QuantiFERON (QIFN) TB-Gold plus assay (Qiagen, Hilden, Germany) are increasingly available substitutes for the TST and are more specific and sensitive.

In this edition of Journal of Investigative Surgery [5], the authors have performed a retrospective study investigating the application of the T-SPOT.TB assay for the early diagnosis of active TB in the CKD patients on immunosuppressive treatment. The authors have included 91 CKD patients receiving immunosuppression for more than 3 months admitted between 2013 and 2016 at their institution in Beijing. The included patients received corticosteroids at two different dose levels (1. Medium/high dose: Prednisone ≥ 30 mg/day administered for four weeks; 2. Low dose: prednisone < 30 mg/day or ≥ 30 mg/day if administered for less than four weeks; or no glucocorticoids). The steroids could be given in combination with other immunosuppressive agents except for rituximab. The study population received T-SPOT.TB tests before and 3 months after the therapy. The authors report two active TB cases and eight with negative results at baseline with positive T-SPOT.TB assay after treatment. No changes in the spot numbers were observed for the patients with positive test at baseline. The authors conclude that increase in the positive T-SPOT.TB results was mainly associated with medium/high doses of the immunosuppression and regular monitoring with T-SPOT.TB assay will help early detection of the active TB.

The current study showed that results of the T-SPOT.TB assay and spot numbers were modified by the immunosuppressants, and there is an increase in the positive tests. Also, in endemic countries like in China, positive T-SPOT.TB assays after immunosuppression could be from new infections.

However, the study is not without its drawbacks. It is a retrospective study with a small number of patients, and thus furthermore extensive studies are needed to validate the findings before widespread clinical application. Also, the IGRAs in general have poor predictive value for active TB in patients with advanced CKD. In a recent systematic review, IGRA appeared to be associated more strongly with clinical risk factors for LTBI, but sensitivity was suboptimal [6].

Pai et al. in a review reported TB incidence rates of 3.7–84.5 cases/1000-person-years in patients with IGRA positive assays and between 2 and 32 cases/1000-person-years in IGRA-negative patients [7]. Larger longitudinal studies are needed comparing the ability of the IGRAs and TST to predict the development of the active TB in CKD patients, before the broader utility of these assays.

As published in the World health organization’s (WHO) 2011–18 guidelines [8], on the use of TB IGRAs in low- and middle-income countries, the IGRA sensitivity for incident TB ranged from 75% to 88% with specificity of 35% to 51%. TST sensitivity for incident TB was similar, ranging from 73% to 76% and specificity was equally low, ranging from 35% to 58%, thus making a recommendation against using the IGRAs or TST to make a diagnosis of the active TB.

Either the TST or IGRAs can be used to test for the LTBI, and IGRAs may be preferred if a patient had a history of BCG immunization after age 1 year and both TST and IGRAs may be performed if the risk of the LTBI is high. Other parameters such as a thorough clinical history, physical examination, and chest x-ray are needed in determining the overall risk of LTBI in the CKD and other immunocompromised patients. In low-income nations, the high per-test cost of the IGRAs compared to TST might limit its usage. However, given significant costs involved, along with burden on the health-care resources in the long-term care of the active TB patients and in contact tracing, one may support the use of the IGRAs given somewhat higher diagnostic sensitivity and specificity. To conclude, the T-SPOT.TB test can be used in the CKD patients on immunosuppression to help detect the early TB infections.

Declaration of interest:

The authors declare that they have no conflicting interest.