First outbreak of multi-drug resistant tuberculosis (MDR-TB) in Denmark involving six Danish-born cases

Background: Denmark is a tuberculosis (TB) and multi-drug resistant (MDR) TB low-incidence country at 5 and 0.05 cases per 100.000 population, respectively. Until 2018, transmission of MDR-TB was nonexistent except for few pairwise related family-cases. In this study we describe the first MDR-TB outbreak in Denmark.
Methods: Based on genotyping of all Mycobacterium tuberculosis (Mtb) culture-positive cases in Denmark spanning three decades, six molecular- and epidemiologically linked Danish-born cases were identified as the first cluster of MDR-TB in Denmark. The primary case was diagnosed posthumously in 2010 followed by five epidemiologically linked cases from 2018 through 2019.
Results and conclusion: Through a combination of routine Mtb genotyping and clinical epidemiological surveillance data, we identified the first Danish MDR-TB outbreak spanning 10 years and were able to disclose the specific transmission pathways in detail guiding the outbreak investigations. The occurrence of an MDR-TB outbreak in a resource rich TB low incidence setting like Denmark, highlights the importance of a collaborative control system combining classical contact tracing; timely identification of drug resistant TB through rapid diagnostics; and a close collaboration between clinicians, classical- and molecular epidemiologists for the benefit of TB control.

Determination of the 161 Tb half-life

There is significant interest in the use of terbium radioisotopes for applications in cancer therapy and diagnosis. Of these, 161Tb, as a medium energy beta-emitter, is being investigated as a potential alternative to 177Lu. The relatively high proportion of conversion electron and Auger electron emissions per decay make 161Tb an attractive targeted therapeutic. As a product of nuclear fission, 161Tb is also of importance to nuclear forensics. The standard uncertainty of the current evaluated half-life of 6.89(2) d contributes significantly to the standard uncertainty of any decay corrected activity determination made.
Furthermore, the accuracy of this evaluated half-life has been called into question by measurements reported in 2020 at the Institute of Radiation Physics (IRA), Switzerland, who reported a half-life of 6.953(2) d. In the current work, the half-life of the 161Tb ground state decay has been measured at three independent laboratories located in the United Kingdom and the United States of America for a total of six determinations using three independent measurement techniques; gamma-ray spectrometry, ionisation chamber measurement and liquid scintillation counting. The half-life determined for 161Tb of 6.9637(29) d confirms the observed 1% relative increase observed by IRA, though the reported half-lives in this work and at IRA are significantly different (ζ-score = 3.1).

Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection

The role of B cells migrating to the lung and forming follicles during tuberculosis (TB) inflammation is still the subject of debate. In addition to their antibody production and antigen-presenting functions, B cells secrete different cytokines and chemokines, thus participating in complex networks of innate and adaptive immunity. Importantly, lung B-cells produce high amounts of the pleiotropic gp130 cytokine IL-6. Its role during TB infection remains controversial, partly due to the fact that IL-6 is produced by different cell types. To investigate the impact of IL-6 produced by B cells on TB susceptibility and immune responses, we established a mouse strain with specific IL-6 deficiency in B cells (CD19cre-IL-6fl/fl, B-IL-6KO) on the B6 genetic background.
Selective abrogation of IL-6 in B cells resulted in shortening the lifespan of TB-infected B-IL-6KO mice compare to the wild-type controls. We provide evidence that at the initial TB stages B cells serve as a critical source of IL-6. In the lung, the effect of IL-6 deficiency in B cells is associated rather with B and T cell functioning, than with macrophage polarization. TB-infected B-IL-6KO mice displayed diminished sizes of B cells themselves, CD4+IFN-γ+, Th17+, and CD4+CXCR5+ follicular T cell populations. The pleiotropic effect of B-cell-derived IL-6 on T-cells demonstrated in our study bridges two major lymphocyte populations and sheds some light on B- and T-cells interactions during the stage of anti-TB response when the host switches on a plethora of acquired immune reactions.

SLC11A1 genetic variation and low expression may cause immune response impairment in TB patients

Tuberculosis (TB) is caused by Mycobacterium tuberculosis. Host genetic factors are important for the detection of TB susceptibility. SLC11A1 is located in monocyte phagolysosomes that help to limit M. tuberculosis growth by transferring divalent cations across the membrane. Genetic variation in SLC11A1 may alter its expression and increase the susceptibility of individuals to TB. The current study aimed to provide insight into host genetic variations and gene expression in TB patients. A total of 164 TB patients and 85 healthy controls were enrolled in this study. SLC11A1 polymorphisms were detected by PCR-RFLP. Real-time qPCR was used for SLC11A1 gene expression, and ELISA was used for protein estimation. GTEx Portal was used for quantitative trait loci analysis, while the STRING (v.11) web platform was used for gene interactive network construction.
Data were analyzed using SPSS, GraphPad Prism, Haploview, and SNPstats. SLC11A1 polymorphisms and combinatorial genotypes were strongly associated with TB susceptibility, which may explain the greater prevalence of tuberculosis in the local population. Polymorphisms in SLC11A1 have also been linked to gene expression variation. Furthermore, the expression of SLC11A1 was downregulated in TB patients, which may influence the function of other associated genes and may impair the immunological response to tuberculosis.

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Evaluation of Diagnostic Microbiology Capacity and Barriers in Testing for HIV and TB at Peripheral Hospital-Based Laboratories in Oyo-State, Nigeria

The prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection in Nigeria is currently around 19.1%. This indicates that the two diseases are still a burden on the nation”s health. The aim of this study was to evaluate the diagnostic microbiology capacity and the barriers in performing assay for TB and HIV at peripheral district-level hospital-based laboratories in Oyo State, Nigeria. Diagnostic microbiology capacity was estimated using a scale of 100-point where scores ≤ 49% were categorized as low, 50-79% fair and ≥80% good. Barriers to diagnosis were summarized in proportions.
The diagnostic microbiology capacity revealed that 6 (35.3%) and 11 (64.7%) of the laboratories had “fair” and “low” capacity, respectively, to detect TB in cerebrospinal fluid/sputum. In testing for HIV, 3 (17.6%) of the laboratories had “fair capacity” and 14 (82.4%) had “low capacity” to detect CD4 count and HIV antibodies in blood serum. The major diagnostic barriers in almost all (94.1%) the laboratories were lack of culture supplies and nonavailability of reagents/testing kits. There was no diagnostic microbiology service with good capacity to facilitate case detection of HIV and TB at the peripheral hospitals. Hence there is a need to improve the supply of reagents, culture stock and testing kits. This will facilitate the detection of TB and HIV cases in peripheral communities. IMPORTANCE This study provided a snapshot knowledge of testing capabilities and commodity availability at state laboratories. The findings should inform the action of stakeholders to improve diagnostic microbiology capacity, consequently enhancing diagnostic measures in detecting human immunodeficiency virus and Mycobacterium tuberculosis.

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