Discordance between TST and QFT-TBGold Plus for Latent Tuberculosis Screening among Under-Five Children: An Interim Analysis

Han

Cytometry Part B Clinical

et al. 2022

Background The interferon‐γ (IFN‐γ) release assay (IGRA) is widely used to diagnose tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb). However, indeterminate IGRA results due to “high Nil” or “low PHA” responses limit its clinical utility. We developed a novel assay using CD69 flow cytometry (FC) to complement IGRA. Methods CD69 FC measures the surface CD69 expression on T cells prior to centrifugation to harvest the plasma for IGRA. T cell responses against Mtb antigen 1 (Ag1) or Ag2 were measured using three‐color FC (CD3, CD4, and CD69) in TB (n = 140) and non‐TB groups (n = 117). The cutoff values of Δ%CD69bright cells (stimulated minus unstimulated) for CD4+ and CD4− T cells were established based on healthy individuals (n = 63). The assay performances of CD69 FC and IGRA were compared. Results In subjects with determinate IGRA results (“positive” or “negative”; n = 216), the diagnostic accuracies of CD69 FC (90.3%) and IGRA (87.0%) were not significantly different (p = 0.31). For indeterminate IGRA results (n = 40), CD69 FC attained a diagnostic accuracy of 92.5%. The CD4+/CD4− ratio within CD69bright T cells measured by CD69 FC was significantly higher (p < 0.05) in the active TB group (6.39 ± 132.05; n = 72) than in other CD69 FC‐positive subjects (2.84 ± 15.36; n = 63) (p < 0.05), whereas CD8 responses expected by IGRA (difference of IFN‐γ levels between Mtb Ag tubes) did not differ significantly (0.00 ± 9.18 and 0.00 ± 4.25, respectively, IU/ml; p = 0.58). Conclusions We demonstrated the potential of CD69 FC as a simple, rapid assay for clarifying indeterminate IGRA results and identifying active TB. With further improvements, CD69 FC may complement the IGRA to enhance TB risk stratification in the routine diagnostic workup.

Section: Discussionmentioning

confidence: 99%

CD69flow cytometry to complement interferon‐γrelease assay for active tuberculosis

Han

Cytometry Part B Clinical

et al. 2022

“…The results of the test could be obtained within 24 h [ 41 ]. The accuracy of IGRAs for children aged <5 years old is still a matter of debate [ 41 , 42 , 43 , 44 ]. However, both TST and IGRA had similar limitations in differentiating ATB and TBI, differentiating recently acquired and old infections, or predicting the progression of TBI to ATB [ 45 ].…”

Section: Screening Tests For Tbimentioning

confidence: 99%

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

et al. 2023

Globally, it is estimated that one-quarter of the world’s population is latently infected with Mycobacterium tuberculosis (Mtb), also known as latent tuberculosis infection (LTBI). Recently, this condition has been referred to as tuberculosis infection (TBI), considering the dynamic spectrum of the infection, as 5–10% of the latently infected population will develop active TB (ATB). The chances of TBI development increase due to close contact with index TB patients. The emergence of multidrug-resistant TB (MDR-TB) and the risk of development of latent MDR-TB has further complicated the situation. Detection of TBI is challenging as the infected individual does not present symptoms. Currently, there is no gold standard for TBI diagnosis, and the only screening tests are tuberculin skin test (TST) and interferon gamma release assays (IGRAs). However, these tests have several limitations, including the inability to differentiate between ATB and TBI, false-positive results in BCG-vaccinated individuals (only for TST), false-negative results in children, elderly, and immunocompromised patients, and the inability to predict the progression to ATB, among others. Thus, new host markers and Mtb-specific antigens are being tested to develop new diagnostic methods. Besides screening, TBI therapy is a key intervention for TB control. However, the long-course treatment and associated side effects result in non-adherence to the treatment. Additionally, the latent MDR strains are not susceptible to the current TBI treatments, which add an additional challenge. This review discusses the current situation of TBI, as well as the challenges and efforts involved in its control.

“…Auch für Kinder unter 15 Jahren liegen inzwischen ausreichend Studiendaten vor, die in dieser Altersgruppe eine vergleichbare Sensitivität des IGRAs gegenüber dem THT belegen [79][80][81][82] und Ersterkrankungen bei immungeschwächten Personen.…”

Section: Tuberkulin-hauttestunclassified

Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose – Update 2023

Diel,

Breuer,

Bös

et al. 2023

Gesundheitswesen

ZusammenfassungZiel der Umgebungsuntersuchung bei Tuberkulose ist neben der aktiven Fallfindung das Aufdecken von Infektionsketten sowie die Verhütung der Weiterverbreitung der Erkrankung. Dabei ist eine sorgfältige Auswahl der Kontaktpersonen notwendig, die sich nach Art und Dauer des Kontaktes richtet, um möglichst frisch Infizierte zu identifizieren und so den Nutzen einer anschließenden präventiven Therapie zu erhöhen und unnötige Testungen von Personen ohne Ansteckungsrisiko zu vermeiden. Seit der letzten Überarbeitung der Empfehlungen zur Umgebungsuntersuchung hat sich die Datenlage zum Einsatz von Interferon-y release-Assays (IGRAs) bei Kindern weiterhin verbessert. Diese werden bevorzugt in der Umgebungsuntersuchung von erwachsenen Kontaktpersonen eingesetzt. Für Kinder unter 15 Jahren können sowohl IGRAs wie auch weiterhin der Tuberkulin-Hauttest gleichwertig verwendet werden. Als präventive Therapie bei nachgewiesener Infektion werden Rifampicin für 4 Monate, Rifampicin und Isoniazid für 3 Monate oder aber Isoniazid für 9 Monate empfohlen.Ausführlich wird auf die Durchführung der Umgebungsuntersuchung in verschiedenen Altersgruppen sowie rechtliche Rahmenbedingungen und sozialmedizinische Aspekte und Herausforderungen eingegangen. Zusätzlich werden Sonderfälle, wie die Umgebungsuntersuchung in Kitas, Schulen oder in anderen Gemeinschaftseinrichtungen, separat dargestellt.