Real-time, portable genome sequencing for Ebola surveillance.

The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10(-3) and 1.42 × 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

Implementation of the 7-1-7 target for detection, notification, and response to public health threats in five countries: a retrospective, observational study.

BACKGROUND: Suboptimal detection and response to recent outbreaks, including COVID-19 and mpox (formerly known as monkeypox), have shown that the world is insufficiently prepared for public health threats. Routine monitoring of detection and response performance of health emergency systems through timeliness metrics has been proposed to evaluate and improve outbreak preparedness and contain health threats early. We implemented 7-1-7 to measure the timeliness of detection (target of ≤7 days from emergence), notification (target of ≤1 day from detection), and completion of seven early response actions (target of ≤7 days from notification), and we identified bottlenecks to and enablers of system performance. METHODS: In this retrospective, observational study, we conducted reviews of public health events in Brazil, Ethiopia, Liberia, Nigeria, and Uganda with staff from ministries of health and national public health institutes. For selected public health events occurring from Jan 1, 2018, to Dec 31, 2022, we calculated timeliness intervals for detection, notification, and early response actions, and synthesised identified bottlenecks and enablers. We mapped bottlenecks and enablers to Joint External Evaluation (second edition) indicators. FINDINGS: Of 41 public health events assessed, 22 (54%) met a target of 7 days to detect (median 6 days [range 0-157]), 29 (71%) met a target of 1 day to notify (0 days [0-24]), and 20 (49%) met a target of 7 days to complete all early response actions (8 days [0-72]). 11 (27%) events met the complete 7-1-7 target, with variation among event types. 25 (61%) of 41 bottlenecks to and 27 (51%) of 53 enablers of detection were at the health facility level, with delays to notification (14 [44%] of 32 bottlenecks) and response (22 [39%] of 56 bottlenecks) most often at an intermediate public health (ie, municipal, district, county, state, or province) level. Rapid resource mobilisation for responses (six [9%] of 65 enablers) from the national level enabled faster responses. INTERPRETATION: The 7-1-7 target is feasible to measure and to achieve, and assessment with this framework can identify areas for performance improvement and help prioritise national planning. Increased investments must be made at the health facility and intermediate public health levels for improved systems to detect, notify, and rapidly respond to emerging public health threats. FUNDING: Bill & Melinda Gates Foundation.

Building National Health Security Through a Rapid Self-Assessment and Annual Operational Plan in Uganda, May to September 2021.

Uganda established a National Action Plan for Health Security in 2019, following a Joint External Evaluation (JEE) of International Health Regulations (2005) capacities in 2017. The action plan enhanced national health security awareness, but implementation efforts were affected by limited funding, excess of activities, and challenges related to monitoring and evaluation. To improve implementation, Uganda conducted a multisectoral health security self-assessment in 2021 using the second edition of the JEE tool and developed a 1-year operational plan. From 2017 to 2021, Uganda's composite ReadyScore improved by 20%, with improvement in 13 of the 19 technical areas. Indicator scores showing limited capacity declined from 30% to 20%, and indicators with no capacity declined from 10% to 2%. More indicators had developed (47% vs 40%), demonstrated (29% vs 20%), and sustained (2% vs 0%) capacities in 2021 compared with 2017. Using the self-assessment JEE scores, 72 specific activities from the International Health Regulations (2005) benchmarks tool were selected for inclusion in a 1-year operational plan (2021-2022). In contrast to the 264 broad activities in the 5-year national action plan, the operational plan prioritized a small number of activities to enable sectors to focus limited resources on implementation. While certain capacities improved before and during implementation of the action plan, countries may benefit from using short-term operational planning to develop realistic and actionable health security plans to improve health security capacities.