Intraspecies genetic diversity has been demonstrated to be important in the pathogenesis and epidemiology of several pathogens, such as HIV, influenza, Helicobacter and Salmonella. It is also important to consider strain-to-strain variation when identifying drug targets and vaccine antigens and developing tools for molecular diagnostics. Here, the authors present a description of the variability in gene expression patterns among ten clinical isolates of Mycobacterium tuberculosis, plus the laboratory strains H37Rv and H37Ra, growing in liquid culture. They identified 527 genes (15 % of those tested) that are variably expressed among the isolates studied. The remaining genes were divided into three categories based on their expression levels: unexpressed (38 %), low to undetectable expression (31 %) and consistently expressed (16 %). The expression categories were compared with functional categories and three biologically interesting gene lists: genes that are deleted among clinical isolates, T-cell antigens and essential genes. There were significant associations between expression variability and the classification of genes as T-cell antigens, involved in lipid metabolism, PE/PPE, insertion sequences and phages, and deleted among clinical isolates. This survey of mRNA expression among clinical isolates of M. tuberculosis demonstrates that genes with important functions can vary in their expression levels between strains grown under identical conditions.

BackgroundDespite considerable efforts to scale up voluntary medical male circumcision (VMMC) for HIV prevention in priority countries over the last five years, implementation has faced important challenges. Seeking to enhance the effect of VMMC programs for greatest and most immediate impact, the U. S. President’s Plan for AIDS Relief (PEPFAR) supported the development and application of a model to inform national planning in five countries from 2013–2014.Methods and FindingsThe Decision Makers’ Program Planning Toolkit (DMPPT) 2.0 is a simple compartmental model designed to analyze the effects of client age and geography on program impact and cost. The DMPPT 2.0 model was applied in Malawi, South Africa, Swaziland, Tanzania, and Uganda to assess the impact and cost of scaling up age-targeted VMMC coverage. The lowest number of VMMCs per HIV infection averted would be produced by circumcising males ages 20–34 in Malawi, South Africa, Tanzania, and Uganda and males ages 15–34 in Swaziland. The most immediate impact on HIV incidence would be generated by circumcising males ages 20–34 in Malawi, South Africa, Tanzania, and Uganda and males ages 20–29 in Swaziland. The greatest reductions in HIV incidence over a 15-year period would be achieved by strategies focused on males ages 10–19 in Uganda, 15–24 in Malawi and South Africa, 10–24 in Tanzania, and 15–29 in Swaziland. In all countries, the lowest cost per HIV infection averted would be achieved by circumcising males ages 15–34, although in Uganda this cost is the same as that attained by circumcising 15- to 49-year-olds.ConclusionsThe efficiency, immediacy of impact, magnitude of impact, and cost-effectiveness of VMMC scale-up are not uniform; there is important variation by age group of the males circumcised and countries should plan accordingly.

In response to World Health Organization (WHO) guidance recommending oral pre-exposure prophylaxis (PrEP) for all individuals at substantial risk for HIV infection, significant investments are being made to expand access to oral PrEP globally, particularly in sub-Saharan Africa. Some have interpreted early monitoring reports from new programs delivering oral PrEP to adolescent girls and young women (AGYW) as suggestive of low uptake. However, a lack of common definitions complicates interpretation of oral PrEP uptake and coverage measures, because various indicators with different meanings and uses are used interchangeably. Furthermore, operationalising these measures in real-world settings is challenged by the difficulties in defining the denominator for measuring uptake and coverage among AGYW, due to the lack of data and experience required to identify the subset of AGYW at substantial risk of HIV infection. This paper proposes an intervention-centric cascade as a framework for developing a common lexicon of metrics for uptake and coverage of oral PrEP among AGYW. In codifying these indicators, approaches to clearly define metrics for uptake and coverage are outlined, and the discussion on ‘low’ uptake is reframed to focus on achieving the highest possible proportion of AGYW using oral PrEP when they need and want it Recommendations are also provided for making increased investments in implementation research to better quantify the sub-group of AGYW in potential need of oral PrEP.and for improving monitoring systems to more efficiently address bottlenecks in the service delivery of oral PrEP to AGYW so that implementation can be taken to scale.

BackgroundIn 2007, the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries across eastern and southern Africa for scaling up voluntary medical male circumcision (VMMC) services. Several years into this effort, we reflect on progress.MethodsUsing the Decision Makers’ Program Planning Tool (DMPPT) 2.1, we assessed age-specific impact, cost-effectiveness, and coverage attributable to circumcisions performed through 2014. We also compared impact of actual progress to that of achieving 80% coverage among men ages 15–49 in 12 VMMC priority countries and Nyanza Province, Kenya. We populated the models with age-disaggregated VMMC service statistics and with population, mortality, and HIV incidence and prevalence projections exported from country-specific Spectrum/Goals files. We assumed each country achieved UNAIDS’ 90-90-90 treatment targets.ResultsMore than 9 million VMMCs were conducted through 2014: 43% of the estimated 20.9 million VMMCs required to reach 80% coverage by the end of 2015. The model assumed each country reaches the UNAIDS targets, and projected that VMMCs conducted through 2014 will avert 240,000 infections by the end of 2025, compared to 1.1 million if each country had reached 80% coverage by the end of 2015. The median estimated cost per HIV infection averted was $4,400. Nyanza Province in Kenya, the 11 priority regions in Tanzania, and Uganda have reached or are approaching MC coverage targets among males ages 15–24, while coverage in other age groups is lower. Across all countries modeled, more than half of the projected HIV infections averted were attributable to circumcising 10- to 19-year-olds.ConclusionsThe priority countries have made considerable progress in VMMC scale-up, and VMMC remains a cost-effective strategy for epidemic impact, even assuming near-universal HIV diagnosis, treatment coverage, and viral suppression. Examining circumcision coverage by five-year age groups will inform countries’ decisions about next steps.