Point-of-care diagnostic tools:Selection, evaluation and implementation in resource-constrained settings

In recent year’s point-of-care diagnostic tools especially for the three main killer diseases HIV/AIDS, tuberculosis and malaria have been emerging on the market. This thesis examines the selection, evaluation and implementation of point-of-care diagnostic tools for use in resource-constrained settings (RCS) where often laboratory capacity is lacking and diagnostic testing is of poor quality. There were two main sub-themes to the work. The first examines diagnostic tests for infectious diseases (chapter 3- 9) and the second sub-theme focuses on point-of-care tests for monitoring disease progression, and tools to monitor treatment side-effects (chapter 10-12). Diagnostics tests for malaria (chapter 3), tuberculosis (chapter 6), HIV (chapter 7) and CD4 counts (chapter 10) have been evaluated and monitored during routine use in RCS. Diagnostic test accuracy evaluations for hepatitis C (chapter 4 and 5), creatinine monitoring (chapter 11) and thyroid stimulating hormone (TSH) (chapter 12) have been carried out under ideal conditions to assess their performance and ease-of-use pre-implementation in RCSs. Furthermore, modelling of diagnostic algorithms has been performed using data from diagnostic accuracy evaluations on HIV tests (chapter 8) in order to select best performing algorithms in 6 different settings in sub-Saharan Africa (chapter 9). Finally, chapter 13 and 14 discuss the main findings of this thesis, give recommendations for policy makers and give recommendation for future studies

Multi-messenger Observations of a Binary Neutron Star Merger

International audienceOn 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim 1.7\,{\rm{s}}$ with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of ${40}_{-8}^{+8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 $\,{M}_{\odot }$. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim 40\,{\rm{Mpc}}$) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position $\sim 9$ and $\sim 16$ days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta