Health leadership and management are essential for ensuring resilient health systems. Relevant training opportunities are often scarce, and the use of digital education could help address this gap. Our aim was to assess the effectiveness of eLearning for healthcare leadership and management capacity building.

The global epidemic of drug-resistant tuberculosis is a catastrophic example of how antimicrobial resistance is undermining the public health gains made possible by combination drug therapy. Recent evidence points to unappreciated bacterial factors that accelerate the emergence of drug resistance. In a genome-wide association study of Mycobacterium tuberculosis isolates from China, we find mutations in the gene encoding the transcription factor prpR enriched in drug-resistant strains. prpR mutations confer conditional drug tolerance to three of the most effective classes of antibiotics by altering propionyl-CoA metabolism. prpR-mediated drug tolerance is carbon-source dependent, and while readily detectable during infection of human macrophages, is not captured by standard susceptibility testing. These data define a previously unrecognized and clinically prevalent class of M. tuberculosis variants that undermine antibiotic efficacy and drive drug resistance.

We estimated long-term tuberculosis (TB) trends in the US population and assessed prospects for TB elimination. We used a detailed simulation model allowing for changes in TB transmission, immigration, and other TB risk determinants. Five hypothetical scenarios were evaluated from 2017 to 2100: 1) maintain current TB prevention and treatment activities (base case); 2) provision of latent TB infection testing and treatment for new legal immigrants; 3) increased uptake of latent TB infection screening and treatment among high-risk populations, including a 3-month isoniazid-rifapentine regimen; 4) improved TB case detection; and 5) improved TB treatment quality. Under the base case, we estimate that by 2050, TB incidence will decline to 14 cases per million, a 52% (95% posterior interval (PI): 35, 67) reduction from 2016, and 82% (95% posterior interval: 78, 86) of incident TB will be among persons born outside of the United States. Intensified TB control could reduce incidence by 77% (95% posterior interval: 66, 85) by 2050. We predict TB may be eliminated in US-born but not non-US-born persons by 2100. Results were sensitive to numbers of people entering the United States with latent or active TB, and were robust to alternative interpretations of epidemiologic evidence. TB elimination in the United States remains a distant goal; however, strengthening TB prevention and treatment could produce important health benefits.

Family Health Strategy, the primary health care program in Brazil, has been scaled up throughout the country, but its expansion has been heterogeneous across municipalities. We investigate if there are unique municipal characteristics that can explain the timing of uptake and the pattern of expansion of the Family Health Strategy from years 1998 to 2012. We categorized municipalities in six groups based on the relative speed of the Family Health Strategy uptake and the pattern of Family Health Strategy coverage expansion. We assembled data for 11 indicators for years 2000 and 2010, for 5,507 municipalities, and assessed differences in indicators across the six groups, which we mapped to examine spatial heterogeneities. Important factors differentiating early and late adopters of the Family Health Strategy were supply of doctors and population density. Sustained coverage expansion was related mainly to population size, marginal benefits of the program and doctors’ supply. The uptake was widespread nationwide with no distinct patterns among regions, but highly heterogeneous at the state and municipal level. The Brazilian experience of expanding primary health care offers three lessons in relation to factors influencing diffusion of primary health care. First, the funding mechanism is critical for program implementation, and must be accompanied by ways to support the supply of primary care physicians in low density areas. Second, in more developed and bigger areas the main challenge is lack of incentives to pursue universal coverage, especially due to the availability of private insurance. Third, population size is a crucial element to guarantee coverage sustainability over time.

Mosaic interspecifically acquired alleles of the multiple transferable resistance () efflux pump operon correlate with increased resistance to azithromycin in in epidemiological studies. However, whether and how these alleles cause resistance is unclear. Here, we use population genomics, transformations, and transcriptional analyses to dissect the relationship between variant alleles and azithromycin resistance. We find that the locus encompassing the transcriptional repressor and the pump is a hot spot of interspecific recombination introducing alleles from and into , with multiple rare haplotypes in linkage disequilibrium at and the promoter region. Transformations demonstrate that resistance to azithromycin, as well as to other antimicrobial compounds such as polymyxin B and crystal violet, is mediated through epistasis between these two loci and that the full-length mosaic allele is required. Gene expression profiling reveals the mechanism of resistance in mosaics couples novel alleles with promoter mutations that increase expression of the pump. Overall, our results demonstrate that epistatic interactions at gained from multiple neisserial species has contributed to increased gonococcal resistance to diverse antimicrobial agents. is the sexually transmitted bacterial pathogen responsible for more than 100 million cases of gonorrhea worldwide each year. The incidence of resistance to the macrolide azithromycin has increased in the past decade; however, a large proportion of the genetic basis of resistance remains unexplained. This study is the first to conclusively demonstrate the acquisition of macrolide resistance through alleles from other species, demonstrating that commensal bacteria are a reservoir for antibiotic resistance to macrolides, extending the role of interspecies mosaicism in resistance beyond what has been previously described for cephalosporins. Ultimately, our results emphasize that future fine-mapping of genome-wide interspecies mosaicism may be valuable in understanding the pathways to antimicrobial resistance. Our results also have implications for diagnostics and public health surveillance and control, as they can be used to inform the development of sequence-based tools to monitor and control the spread of antibiotic-resistant gonorrhea.