Potential application of digitally linked tuberculosis diagnostics for real-time surveillance of drug-resistant tuberculosis transmission: Validation and analysis of test results

YesBackground: Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance. Objective: We aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission. Methods: We selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance–determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains’ available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission. Results: The RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers’ claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A, Bdelayed, C, and Edelayed; Genotype MTBDRplus v2.0 WT2, WT5, and WT6; and Genoscholar NTM + MDRTB II S1 and S3. Inspection of probe reactions of disputed mutations may potentially resolve discordance between genotypic and phenotypic test results. Conclusions: We propose a novel approach for potential real-time detection of RR-TB transmission through fully using digitally linked TB diagnostics and shared repository of test results. To our knowledge, this is the first pragmatic and scalable work in response to the consensus of world-renowned TB experts in 2016 on the potential of diagnostic connectivity to accelerate efforts to eliminate TB. This is evidenced by the ability of our proposed approach to facilitate comparison of probe reactions between different RDTs used in the same setting. Integrating this proposed approach as a plug-in module to a connectivity platform will increase usefulness of connected TB diagnostics for RR-TB outbreak detection through real-time investigation of suspected RR-TB transmission cases based on epidemiologic linking.KCN was supported by Erasmus Mundus Joint Doctorate Fellowship grant 2016-1346, and BCdJ, LR, and CJM were supported by European Research Council-INTERRUPTB starting grant 311725

Synthesis, crystallographic data, solubility and electrokinetic properties of copper-, nickel- and cobalt˗uranylphosphate

A discussion is given concerning the transformation in acid medium of curite into copper-, nickel-and cobalt-uranylphosphate. From chemical, differential thermal and thermogravimetric analyses, the crystal-chemical formula are calculated as : Cu (UO₂/PO₄)₂ • 8 H₂O, Ni (UO₂/PO₄)₂ • 7 H₂O and Co (UO₂/PO₄)₂ • 7 H₂O. The two last compounds crystallize in the triclinic system with space group P1 or P[-1]. The cell parameters are calculated as : a = 6.975 Å ; b = 6.938 Å ; c = 10.700 Å ; α = 106.2° ; β = 104.8° ; γ = 90.3° for Ni (UO₂/PO₄)₂ • 7 H₂O and as : a = 7.007 Å ; b = 6.981 Å ; c = 9.105 Å ; α = 102.6° ; β = 106.1° ; γ = 90.4° for Co (UO₂/PO₄)₂ • 7 H₂Ο. Cu (UO₂/PO₄)₂ • 8 H₂O crystallizes in the tetragonal system with space group P4/nmm and the cell parafneters are calculated as : a = b = 6.969 Å et c = 17.306 Å. From solubility data, the solubility products are computed as 10exp[-12.8], 10exp[-9.5] and 10exp[-9.9] for the copper-, nickel-and cobalt-compound respectively. The electrokinetic properties of the three species are closely similar to those of natural meta-torbernite : the zeta-potential is negative and the point of zero charge cannot be reached in the pH-range 2 to 9.Une discussion est consacrée à la transformation en milieu acide de curite en phosphate d'uranyle de cuivre, de nickel et de cobalt. A partir d'analyses chimiques, thermodifférentielles et thermogravimétriques, les formules cristallo-chimiques calculées sont Cu (UO₂/PO₄)₂ • 8 H₂O, Ni (UO₂/PO₄)₂ • 7 H₂O et Co (UO₂/PO₄)₂ • 7 H₂O. Les deux derniers produits cristallisent dans le système triclinique, groupe spatial P1 ou P[-1]. Les paramètres de la maille valent : a = 6,975 Å ; b = 6,938 Å ; c = 10,700 Å ; α = 106,2° ; β = 104,8° ; γ = 90,3° pour Ni (UO₂/PO₄)₂ • 7 H₂O et a = 7,007 Å ; b = 6,981 Å ; c = 9,105 Å ; α = 102,6° ; β = 106,1° ; γ = 90,4° pour Co (UO₂/PO₄)₂ • 7 H₂Ο. Cu (UO₂/PO₄)₂ • 8 H₂O cristallise dans le système quadratique, groupe spatial P4/nmm et les paramètres de la maille valent : a = b = 6,969 Å et c = 17,306 Å. D'après les mesures de la solubilité, les produits de solubilité ont été calculés comme : 10exp[-12,8], 10exp[-9,5] et 10exp[-9,9] respectivement pour les phosphates d'uranyl de cuivre, de nickel et de cobalt. Les propriétés électrocinétiques de ces trois produits ressemblent à celles de la métatorbernite naturelle : le potentiel zéta est négatif et le point de charge électrique nul ne peut pas être atteint dans l'intervalle de pH de 2 à 9.Vochten Renaud, Piret Paul, Goeminne André. Synthesis, crystallographic data, solubility and electrokinetic properties of copper-, nickel- and cobalt˗uranylphosphate. In: Bulletin de Minéralogie, volume 104, 4, 1981. 12e assemblée générale de l'I.M.A. - Orléans – Juillet 1980. Deuxième partie : inclusions magmatiques / silicates / gemmes / « open session »