Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube.

BACKGROUND: The screening and treatment of latent tuberculosis (TB) infection reduces the risk of progression to active disease and is currently recommended for HIV-infected patients. The aim of this study is to evaluate, in a low TB incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen Heparin-Binding Haemagglutinin (HBHA-IGRA), to the detection of Mycobacterium tuberculosis infection in HIV-infected patients. METHODS: Treatment-naïve HIV-infected adults were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the HBHA-IGRA in parallel to a classical method consisting of medical history, chest X-ray, tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT). Prospective clinical and biological follow-up ensued, with repeated testing with HBHA-IGRA. A group of HIV-infected patients with clinical suspicion of active TB was also recruited and tested with the HBHA-IGRA. Multiplex analysis was performed on the culture supernatants of this in-house assay to identify test read-outs alternative to interferon-gamma that could increase the sensitivity of the test. RESULTS: Among 48 candidates enrolled for screening, 9 were identified with latent TB by TST and/or QFT-GIT results. Four of these 9 patients and an additional 3 screened positive with the HBHA-IGRA. This in-house assay identified all the patients that were positive for the TST and showed the best concordance with the presence of a M. tuberculosis exposure risk. During follow-up (median 14 months) no case of active TB was reported and HBHA-IGRA results remained globally constant. Fourteen HIV-infected patients with clinical suspicion of active TB were recruited. Active TB was confirmed for 6 of them among which 3 were HBHA-IGRA positive, each with very high interferon-gamma concentrations. All patients for whom active TB was finally excluded, including 2 non-tubercular mycobacterial infections, had negative HBHA-IGRA results. Multiplex analysis confirmed interferon-gamma as the best read-out. CONCLUSIONS: The HBHA-IGRA appears complementary to the QuantiFERON-TB Gold In-Tube for the screening of latent TB in HIV-infected patients. Large-scale studies are necessary to determine whether this combination offers sufficient sensitivity to dismiss TST, as suggested by our results. Furthermore, HBHA-IGRA may help in the diagnosis work-up of clinical suspicions of active TB.

Evaluation and Modelling of the Performance of an Automated SARS-CoV-2 Antigen Assay According to Sample Type, Target Population and Epidemic Trends.

The Lumipulse® G SARS-CoV-2 Ag assay performance was evaluated on prospectively collected saliva and nasopharyngeal swabs (NPS) of recently ill in- and outpatients and according to the estimated viral load. Performances were calculated using RT-PCR positive NPS from patients with symptoms ≤ 7 days and RT-PCR negative NPS as gold standard. In addition, non-selected positive NPS were analyzed to assess the performances on various viral loads. This assay yielded a sensitivity of 93.1% on NPS and 71.4% on saliva for recently ill patients. For NPS with a viral load > 103 RNA copies/mL, sensitivity was 96.4%. A model established on our daily routine showed fluctuations of the performances depending on the epidemic trends but an overall good negative predictive value. Lumipulse® G SARS-CoV-2 assay yielded good performance for an automated antigen detection assay on NPS. Using it for the detection of recently ill patients or to screen high-risk patients could be an interesting alternative to the more expensive RT-PCR.

Clinical value of FDG-PET/CT for the diagnosis of human immunodeficiency virus-associated fever of unknown origin: a retrospective study.

AIM: The aim of this study was to evaluate retrospectively the usefulness of [18F]fluorodeoxyglucose (FDG)-PET/ computed tomography (CT) in patients affected by human immunodeficiency virus and suffering from fever of unknown origin (HIV-associated FUO). MATERIAL AND METHODS: Ten patients (six males, four females, age 24-48 years) suffering from HIV-associated FUO were studied by FDG-PET/CT. Final diagnosis was established either by microbiological or histopathological analysis or by a more than 6-month follow-up. FDG-PET/CT was regarded as 'helpful for diagnosis' when the abnormal uptake pointed to the organ or location where the cause of fever was thereafter identified. RESULTS: Nine out of 10 FDG-PET/CT were abnormal and the cause of fever was further demonstrated by other diagnostic procedures. An infectious process (tuberculosis) was diagnosed in six patients and a neoplasm in three (two lymphomas, one Kaposi's sarcoma). FDG-PET/CT directly suggested sites for biopsy in six patients (tuberculous lymphadenitis and neoplasm). The only patient with normal FDG-PET/CT suffered from drug-induced fever. CONCLUSION: FDG-PET/CT is a valuable tool in patients with HIV-associated FUO. FDG-PET/CT was categorized as 'helpful for diagnosis' in nine out of the 10 patients we studied. Adding the CT anatomical landmarks to the PET findings allowed an accurate and easy localization of the sites to be punctured in the six patients in whom histopathological diagnosis was needed.

Diversity of life-threatening complications due to Mediterranean spotted fever in returning travelers.

BACKGROUND: Mediterranean spotted fever (MSF) is a tick-borne infection caused by Rickettsia conorii conorii mainly endemic in the Mediterranean Basin. Although usually considered as a benign disease, severe forms of MSF have been sporadically reported. METHODS: We report on three patients who developed severe MSF complications after a stay in Morocco. Literature was reviewed to assess the frequency and pattern of MSF complications in the largest reported case series in endemic countries. RESULTS: Each of our three patients diagnosed with MSF presented with a different complicated course: one with meningoencephalitis, one with lung embolism and one with septic shock and multi organ failure. In published series, rate of complications (defined as severe organ involvement) ranged from 1% to 20%. However, study designs and settings were highly variable and did not allow for relevant comparisons. Meningoencephalitis and shock with multi organ failure were the most frequently observed complications. Mortality of severe course was up to 20% in some series. CONCLUSION: Severe organ involvement is not infrequent in patients with Mediterranean spotted fever and fatal outcome is regularly reported. Because presentations of complicated course may be extremely diverse, a high index of suspicion is required in febrile patients with potential exposure, in particular if skin rash and/or eschar are found. Early appropriate antibiotherapy is crucial to improve outcome.

Regulatory T cells depress immune responses to protective antigens in active tuberculosis.

RATIONALE: Tuberculosis (TB) remains a leading cause of death, and the role of T-cell responses to control Mycobacterium tuberculosis infections is well recognized. Patients with latent TB infection develop strong IFN-gamma responses to the protective antigen heparin-binding hemagglutinin (HBHA), whereas patients with active TB do not. OBJECTIVES: We investigated the mechanism of this difference and evaluated the possible involvement of regulatory T (Treg) cells and/or cytokines in the low HBHA T-cell responses of patients with active TB. METHODS: The impact of anti-transforming growth factor (TGF)-beta and anti-IL-10 antibodies and of Treg cell depletion on the HBHA-induced IFN-gamma secretion was analyzed, and the Treg cell phenotype was characterized by flow cytometry. MEASUREMENTS AND MAIN RESULTS: Although the addition of anti-TGF-beta or anti-IL-10 antibodies had no effect on the HBHA-induced IFN-gamma secretion in patients with active TB, depletion of CD4(+)CD25(high)FOXP3(+) T lymphocytes resulted in the induction by HBHA of IFN-gamma concentrations that reached levels similar to those obtained for latent TB infection. No effect was noted on the early-secreted antigen target-6 or candidin T-cell responses. CONCLUSIONS: Specific CD4(+)CD25(high)FOXP3(+) T cells depress the T-cell-mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.