Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.

The publication of studies using next generation sequencing to analyse large numbers of bacterial isolates from global epidemics is transforming microbiology, epidemiology and public health. The emergence of multidrug resistant Salmonella Typhimurium ST313 is one example. While the epidemiology in Africa appears to be human-to-human spread and the association with invasive disease almost absolute, more needs to be done to exclude the possibility of animal reservoirs and to transfer the ability to track all Salmonella infections to the laboratories in the front line. In this mini-review we summarise what is currently known about non-typhoidal Salmonella in sub-Saharan Africa and discuss some of the issues which remain.

BackgroundInvasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent.MethodsA total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010–2014) and a fever study in Ghana (2007–2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes–genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site.ResultsSalmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries.ConclusionsWe identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.

The interplay between tuberculosis and depression has been problematic since the humoralists. Over the centuries similarities in disease management have transpired. With the advent of isoniazid chemotherapy, transformation of tuberculosis patients from morbidly depressive to euphoric was noted. Isoniazid was thereafter widely prescribed for depression: hepatotoxicity ending its use as an antidepressant in 1961. Isoniazid monotherapy led to the emergence of drug resistant tuberculosis, stimulating new drug development. Vastly increased investment into antidepressants ensued thereafter while investment in new drugs for tuberculosis lagged. In the 21st century, both diseases independently contribute significantly to global disease burdens: renewed convergence and the resultant syndemic is detrimental to both patient groups. Ending the global tuberculosis epidemic and decreasing the burden of depression and will require multidisciplinary, patient-centered approaches that consider this combined co-morbidity. The emerging era of big data for health, digital interventions and novel and repurposed compounds promise new ways to treat both diseases and manage the syndemic, but absence of clinical structures to support these innovations may derail the treatment programs for both. New policies are urgently required optimizing use of the current advances in healthcare available in the digital era, to ensure that patient-centered care takes cognizance of both diseases.