Implementation and evaluation of new tools for Ebola virus disease response during outbreaks in eastern Democratic Republic of the Congo: from rapid diagnostic tests to genomic sequencing.

The Democratic Republic of the Congo has faced fifteen Ebola virus disease (EVD) outbreaks, among which the 2018-2020 was the most widespread and deadliest so far. During that outbreak associated with chronic insecurity, community mistrust and resistance, thirteen field laboratories were deployed to support the EVD diagnosis with the GeneXpert. As this latter cannot be used everywhere in remote areas due to its additional requirements, rapid diagnostic tests (RDTs) were proposed as an alternative tool to support quick decision-making at the point-of-care. However, questions regarding RDTs diagnostic performance and usability were raised due to their disparate performances. In the first part of this PhD thesis, we showed how decentralized and strategically positioned diagnostic laboratories quickly helped to mitigate the risk of Ebola virus spread through rapid, efficient, accurate and well-structured response. Quick hand over of competences and capacities to local teams led to successful management of further health emergencies (EVD flare-ups and Covid-19 pandemic), as those laboratories had dedicated equipment and well-trained local personnel. Sequencing data guided public health decision-making, helped understanding the outbreak dynamics, at risk populations and exposed health zones. In the second part of this PhD, QuickNaviTM RDT had high specificity and quite good sensitivity than OraQuick and Coris tests in outbreaks conditions. QuickNavi-EbolaTM was less impressive compared to previous studies; OraQuick test was almost in line with previous findings, although it performed better for the middle and lower Ct-values in laboratory conditions. None of the four Ebola RDTs evaluated throughout our studies, achieved the desired (sensitivity >98%, specificity >99%) or acceptable (sensitivity >95%, specificity >99%) levels of performance as stated by the WHO Target Product Profile for EBOV tests. However, respective specificities of the QuickNaviTM (>99%) and OraQuick Ebola (98%) in most our studies were close to the acceptable level of performance (>99%). Based on overall performances, QuickNaviTM and Oraquick Ebola RDTs were proposed as a screening panel at the point-of-care to triage and isolate suspect-cases waiting for the RT-qPCR results. RDTs results expectancy will be done separately i.e. individuals with at least one positive RDT isolated in the high-risk area and those with negative RDTs results in low-risk area. For postmortem surveillance, OraQuick RDT effectively complemented the response efforts, improved the community engagement, and decreased the number of systematic safe and dignified burials (SDBs) in corpses with non-reactive test. Trust towards postmortem testing led families to voluntarily request for SDBs despite OraQuick non-reactive results.