On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens.

Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to neutralize the virus in vitro and prevent disease in animal challenge models on reexposure. However, the current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. The COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike protein (S), receptor-binding domain, and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Meso Scale Discovery Assay. Survival analysis determined the proportion of seroreversion, while 2 hierarchical gamma models predicted the upper and lower bounds of long-term antibody trajectory. A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days after symptoms, >95% of participants had detectable S antibodies, compared with 75% with detectable N antibodies. S antibody was predicted to remain detectable in 95% of participants until 465 days (95% confidence interval, 370–575 days) using a “continuous-decay” model and indefinitely using a “decay-to-plateau” model to account for antibody secretion by long-lived plasma cells. S-antibody titers were correlated strongly with surrogate neutralization in vitro (R² = 0.72). N antibodies, however, decayed rapidly with a half-life of 60 days (95% confidence interval, 52–68 days). The Co-Stars data presented here provide evidence for long-term persistence of neutralizing S antibodies. This has important implications for the duration of functional immunity after SARS-CoV-2 infection. In contrast, the rapid decay of N antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics after SARS-CoV-2 infection. NCT04380896.

There are an estimated 10 million new cases of tuberculosis worldwide annually, with 282,000 new or relapsed cases each year reported from the Americas. With improvements in genome sequencing technology, it is now possible to study the genetic diversity of tuberculosis with much greater resolution. Although tuberculosis bacteria do not engage in horizontal gene transfer, the genome is far more variable than previously thought. The study of genome-wide variation in tuberculosis has improved our understanding of the evolutionary origins of tuberculosis, the arrival of tuberculosis in Latin America, the genetic determinants of drug resistance, and lineage-specific associations with important clinical phenotypes. This article reviews what is known about the arrival of tuberculosis in Latin America, the genetic diversity of tuberculosis in Latin America, and the genotypic determinants of clinical phenotypes.

Introduction: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) specific antibodies have been shown to neutralize the virus in-vitro. Understanding antibody dynamics following SARS-CoV-2 infection is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies is also vital for large seroprevalence surveys which inform government policies and public health interventions. However, rapidly waning antibodies following SARS-CoV-2 infection could jeopardize the sensitivity of serological testing on which these surveys depend. Methods: This prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody titers were quantified to the SARS-CoV-2 nucleoprotein (N), spike (S-)protein and the receptor-binding-domain (RBD) of the S-protein. Titers were log-transformed and a multivariate log-linear model with time-since-infection and clinical variables was fitted by Bayesian methods. Results: The mean estimated half-life of the N-antibody was 52 days (95% CI 42-65). The S- and RBD-antibody had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD-antibody titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N-antibody test for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236). Discussion: After SARS-CoV-2 infection, the predicted half-life of N-antibody was 52 days with 50% of seropositive participants becoming seronegative to this antibody at 195 days. Widely used serological tests that depend on the N-antibody will therefore significantly underestimate the prevalence of infection following the majority of infections. Significance statement: We believe that our study has significant and urgent public health and translational impact. Firstly, our findings demonstrate that the half-life of the SARS-CoV-2 nucleoprotein antibody is only 52 days. This has immediate and important implications for large-scale seroprevalence surveys, government policy and mathematical modelling predictions which rely on serological tests that target this antibody. Secondly, the slower decay of the SARS-CoV-2 spike protein antibody identified in this study makes assays to the spike protein a more reliable target for serological assays in the longer term. We demonstrate a strong positive linear correlation between spike/RBD antibody and ACE-2 receptor binding in vitro. Our findings are therefore likely to reflect the time to loss of a functional antibody response in SARS-CoV-2. Funding: GOSH charity, Wellcome Trust (201470/Z/16/Z and 220565/Z/20/Z). GOSH NIHR Funded Biomedical Research Centre. Trial registration number: NCT04380896.

Many studies have demonstrated that prisons are hotspots of tuberculosis disease and transmission. Despite this, it remains unclear which interventions are most effective at controlling tuberculosis in prisons. The objective was to determine the study designs used to investigate tuberculosis control in prisons, and the efficacy of interventions undertaken. This systematic review included published studies which had the aim of reducing TB incidence or prevalence, or increasing the number of people screened for active pulmonary tuberculosis in incarcerated populations. 2,429 records were identified, 178 full-text articles were screened, and 17 studies included. The majority of reports were before/after or prospective non-comparative studies. The median study duration was 23 months (range 5-144). The most common intervention was the introduction of active case finding (10/17 studies) but the timing and methods varied. Comparable pre- and post intervention outcome values were infrequently reported; therefore, it was not possible to quantify the efficacy of interventions. Data from studies of tuberculosis control in prisons is limited by a lack of: controlled interventions, reporting of pre-intervention methods, and comparable pre- and post-intervention outcomes. Prospective comparative trials of adequate duration to determine trends in incidence are necessary to understand which interventions are effective in prisons.