Interferon Gamma Release Assay and Tuberculin Skin Test Agreement for the Diagnosis of Latent Tuberculosis in HTLV-1 Subjects

Background: Diagnosis and treatment of latent tuberculosis infection (LTBi) among HTLV-1 subjects is clinically relevant based on increased risk of active TB and TB-associated mortality. Interferon gamma release assay (IGRA) is validated to measure the differential IFN-γ production under nil, mitogen-stimulated and TB antigen-stimulated conditions. However, spontaneous production of IFN-γ induced by HTLV-1 (Th1 immunologic response) may increase the proportion of indeterminate results in co-infected patients. We assess the agreement between IGRA and Tuberculin Skin Test (TST) for LTBi diagnosis in HTLV-1 subjects in an endemic country.

Methods: We enrolled 39 HTLV-1 subjects (18-65 years old) without prior history or evidence of active tuberculosis at our Institute (referral center for HTLV-1 patients in Peru). TST results (positive if >10 mm) were obtained from medical records; if negative or unavailable a new TST was performed. Peripheral blood was drawn for Quantiferon TB Gold testing (IGRA) following manufacturer’s instructions (reported as positive, negative or indeterminate). Descriptive statistics and a concordance analysis were performed.Results: Clinical characteristics (Table 1) and TST-IGRA results are displayed (Table 2). Positive TST was greater among patients with positive IGRA (p value <0.05). IGRA performed well in this subjects; no indeterminate results were reported. 32 observed agreements between IGRA and TST were reported (82.05%, Kappa 0.65, standard error 0.15). Six out of seven of the discordant results were TST positive and IGRA negative. Non-discordant patients had a greater history of TB contact compared with discordant patients (10 vs. 5, p = 0.048).

Table 1. Clinical Characteristics

	Positive IGRA (n = 17)	Negative IGRA (n = 22)	p value
Male	6	7	0.89
Associated HTLV-1 complication	12	13	0.45
Steroid treatment in past 6 months	3	1	0.18
Positive TST	16	6	<0.05*
History of TB contact	6	9	0.72

Table 2. IGRA and TST results

		TST
		Positive	Negative	Total
IGRA	Positive	16	1	17
	Negative	6	16	22
	Total	22	17	39

Conclusion: Moderate agreement between IGRA and TST was found. The higher TST frequency may be explained due to routine BCG vaccination policy in our country. Interestingly, prior TB contact was associated with agreement between tests. IGRA could be a reasonable alternative for LTBi diagnosis in the HTLV-1 population.