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Seasonal influenza viruses are constantly changing and produce a different set of circulating strains each season. Small genetic changes can accumulate over time and result in antigenically different viruses; this may prevent the body’s immune system from recognizing those viruses. Due to rapid mutations, in particular, in the haemagglutinin (HA) gene, seasonal influenza vaccines must be updated frequently. This requires choosing strains to include in the updates to maximize the vaccines’ benefits, according to estimates of which strains will be circulating in upcoming seasons. This is a challenging prediction task. In this paper, we use longitudinally sampled phylogenetic trees based on HA sequences from human influenza viruses, together with counts of epitope site polymorphisms in HA, to predict which influenza virus strains are likely to be successful. We extract small groups of taxa (subtrees) and use a suite of features of these subtrees as key inputs to the machine learning tools. Using a range of training and testing strategies, including training on H3N2 and testing on H1N1, we find that successful prediction of future expansion of small subtrees is possible from these data, with accuracies of 0.71–0.85 and a classifier ‘area under the curve’ 0.75–0.9.

de la comunicación oral presentada al Scientific Meeting on Mycobacteria. MycoPORTO 2019 Porto (Portugal), 19-20 de septiembre de 2019, Pág. 23 del libro de abstracts que se adjunta. With around 10 million new cases per year, tuberculosis (TB) is one of the most important infectious diseases in the world. Whole genome sequencing (WGS) is often used in TB surveillance programs due to its greater resolution compared to classical typing methods. Studies have demonstrated that WGS can identify outbreaks, predict transmission events and distinguish between relapses and co-infections. Despite this, the directionality of the transmission (whom infected whom) remains still uncertain. Here, we used WGS to identify, characterize and infer TB transmission in a low-incidence country during a three-year period. We applied phylogeographic approaches to identify and determine the date of endemic phylogenetic groups that are associated with Spanish-born transmission. Using pairwise nucleotide distances, we show a low concordance between WGS transmission and standard contact tracing method (40% vs 12.5%). Furthermore, we developed a model by combining epidemiological and genomic data to obtain estimates of the number of index cases and missing cases within clusters. This study improves the understanding of how and when TB transmits. In addition, it highlights the relevance of WGS data for improving disease control.

Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modelling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first three months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods’ development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.

Trees that illustrate patterns of ancestry and evolution are a central tool in many areas of biology. Comparing evolutionary trees to each other has widespread applications in comparing the evolutionary stories told by different sources of data, assessing the quality of inference methods, and highlighting areas where patterns of ancestry are uncertain. While these tasks are complicated by the fact that trees are high-dimensional structures encoding a large amount of information, there are a number of metrics suitable for comparing evolutionary trees whose tips have the same set of unique labels. There are also metrics for comparing trees where there is no relationship between their labels: in ‘unlabelled’ tree metrics the tree shapes are compared without reference to the tip labels.In many interesting applications, however, the taxa present in two or more trees are related but not identical, and it is informative to compare the trees whilst retaining information about their tips’ relationships. We present methods for comparing trees whose labels belong to a pre-defined set of categories. The methods include a measure of distance between two such trees, and a measure of concordance between one such tree and a hierarchical classification tree of the unique categories. We demonstrate the intuition of our methods with some toy examples before presenting an analysis ofMycobacterium tuberculosistrees, in which we use our methods to quantify the differences between trees built from typing versus sequence data.

International audience; To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the “Phylogenetics and Networks for Generalised HIV Epidemics in Africa” consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n = 2,833; MRC/UVRI Uganda, n = 701; Mochudi Prevention Project, n = 359; Africa Health Research Institute Resistance Cohort, n = 92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3′ end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences (NGS) has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

The implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http:// www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show that in silico predictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) communityoriented database infrastructure and analysis tools. IMPORTANCE The spread of antibiotic-resistant bacteria is a public health emergency of global concern, threatening medical intervention at every level of health care delivery. Several recent studies have demonstrated the promise of routine wholegenome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control. However, as this technology becomes more widely adopted, the key challenges of generating representative national and international data sets and the development of bioinformatic tools to manage and interpret the data become increasingly pertinent. This study provides a road map for the integration of WGS data into routine pathogen surveillance. We emphasize the importance of large-scale routine surveys to provide the population context for more targeted or localized investigation and the development of open-access bioinformatic tools to provide the means to combine and compare independently generated data with publicly available data sets.

Background Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. Methods We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. Results Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. Conclusions As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission. Electronic supplementary material The online version of this article (doi:10.1186/s12916-016-0566-x) contains supplementary material, which is available to authorized users.