Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

Abstract

Abstract. Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis. The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD ® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem ® ). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.

Accuracy of interferon-γ-induced protein 10 for diagnosing latent tuberculosis infection: a systematic review and meta-analysis

“…Latorre et al found that the positive rates for children exposed to patients with active TB were 45.7% for the QFT-IT, 46.9% for the IP-10 test, and 50.6% for QFT-IT and IP-10 tests [37]. Drabe et al reported that the positive detection rate for the IP-10 test was higher than that of the QFT-IT test for diagnosing LTBI in immunocompromised individuals (30% and 25%, respectively) [38]. For the populations at high risk of progressing from LTBI to active TB, the IP-10 test could be an additional test for the general screening programme (TSTs and IGRAs) to diagnose LTBI.…”

Positive Correlation between IP-10 and IFN-γLevels in Rhesus Monkeys(Macaca mulatta)with Either Naturally Acquired or Experimental Infection ofMycobacterium tuberculosis

“…IP-10 has been investigated in human tuberculosis patients and bovine tuberculosis. Most reports supported that the diagnostic accuracy of IP-10 was to be on par with IFN- γ release assays (IGRAs) [ 6 , 17 – 20 ].…”

Elevated Spontaneous Interferon-γ Secretion in Human Immunodeficiency Virus-Infected Persons

“…The QFT nil values have previously been reported in several studies, including in the setting of US healthcare workers who converted from negative to positive IGRA [ 9 ], malaria infection in HIV-positive subjects [ 10 ], and in subjects with repeat IGRA tests [ 11 ]. Our report adds to this growing body of knowledge, and it is possible that the QFT nil value will have increased clinical and/or epidemiologic utility as it is further explored in a greater number of populations.…”