Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

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Nasopharyngeal carriage studies provide insights into the local prevalence of circulating pneumococcal serotypes. These data are critical to vaccination monitoring, as they allow for the prediction and assessment of impact. Very little data are available on the carriage of pneumococcal serotypes in Morocco. Here, we describe the prevalence of Streptococcus pneumoniae carriage and serotype distribution among 697 pediatric patients with ages ranging from 2 to 59 months who were admitted to a Moroccan hospital with severe pneumonia, as well as 195 healthy infants and young children who were recruited at a vaccination clinic. Carriage rates were 40.5% (79/195) for healthy children and 22.8% (159/697) for sick children. The most commonly observed circulating serotypes included 6A, 6B and 19F, all of which are included in the current 13-valent anti-pneumococcal conjugate vaccine that was recently introduced in Morocco. Monitoring of circulating serotypes remains necessary after vaccine introduction to assess whether serotype replacement is occurring.

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SummaryBackgroundPneumococcal Conjugate Vaccine (PCV) which targets up to 13 serotypes of Streptococcus pneumoniae is very effective at reducing disease in young children; however, rapid increases in replacement with non-PCV serotypes remains a concern. Serotype 24F is one of the major invasive serotypes that mediates serotype replacement in France and multiple other countries. We aimed to identify the major pneumococcal lineage that has driven the increase of serotype 24F in France, and provide context for the findings by investigating the global diversity of serotype 24F pneumococci and characterise the driver lineage from a global perspective and elucidate its spatiotemporal transmission in France and across the world.MethodsWe whole-genome sequenced a collection of 419 serotype 24F S. pneumoniae from asymptomatic carriers and invasive disease cases among individuals <18 years old in France between 2003 and 2018. Genomes were clustered into Global Pneumococcal Sequence Clusters (GPSCs) and clonal complexes (CCs) so as to identify the lineages that drove the increase in serotype 24F in France. For each serotype 24F lineage, we evaluated the invasive disease potential and propensity to cause meningitis by comparing the proportion of invasive disease cases with that of carriers. To provide a global context of serotype 24F and the driver lineage, we extracted relevant genomes and metadata from the Global Pneumococcal Sequencing (GPS) project database (n=25,590) and additionally sequenced a collection of 91 pneumococcal isolates belonging to the lineage that were responsible for the serotype 24F increase in Spain during the PCV introduction for comparison. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted to understand the mechanism underlying the global spread of serotype 24F, evolutionary history and long-range transmissions of the driver lineage.FindingsA multidrug-resistant pneumococcal lineage GPSC10 (CC230) drove the serotype 24F increase in both carriage and invasive disease in France after PCV13 introduction. When compared with other serotype 24F lineages, it exhibited a 1.4-fold higher invasive disease potential and 1.6-fold higher propensity to cause meningitis. Globally, serotype 24F was widespread, largely due to clonal dissemination of GPSC10, GPSC16 (CC66) and GPSC206 (CC7701) rather than recent capsular switching. Among these lineages, only GPSC10 was multidrug-resistant. It expressed 17 serotypes, with only 6 included in PCV13 and none of the expected PCVs covered all serotypes expressed by this lineage. Global phylogeny of GPSC10 showed that all serotype 24F isolates except for one were clustered together, regardless of its country of origin. Long-range transmissions of GPSC10-24F from Europe to Israel, Morocco and India were detected. Spatiotemporal analysis revealed that it took ∼5 years for GPSC10- 24F to spread across French provinces. In Spain, we detected that the serotype 24F driver lineage GPSC10 underwent a rapid change of serotype composition from serotype 19A to 24F during the introduction of PCV13 (targets 19A but not 24F), indicating that pre-existence of serotype variants enabled GPSC10 to survive and expand under vaccine-selective pressure.InterpretationOur work further shows the utility of bacterial genome sequencing to better understand the pneumococcal lineages behind the serotype changes and reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases.FundingBill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.