RESUMO
Despite efforts to eliminate malaria in Sao Tome and Principe (STP), cases have recently increased. Understanding residual transmission structure is crucial for developing effective elimination strategies. This study collected surveillance data and generated amplicon sequencing data from 980 samples between 2010 and 2016 to examine the genetic structure of the parasite population. The mean multiplicity of infection (MOI) was 1.3, with 11% polyclonal infections, indicating low transmission intensity. Temporal trends of these genetic metrics did not align with incidence rates, suggesting that changes in genetic metrics may not straightforwardly reflect changes in transmission intensity, particularly in low transmission settings where genetic drift and importation have a substantial impact. While 88% of samples were genetically linked, continuous turnover in genetic clusters and changes in drug-resistance haplotypes were observed. Principal component analysis revealed some STP samples were genetically similar to those from Central and West Africa, indicating possible importation. These findings highlight the need to prioritize several interventions such as targeted interventions against transmission hotspots, reactive case detection, and strategies to reduce the introduction of new parasites into this island nation as it approaches elimination. This study also serves as a case study for implementing genetic surveillance in a low transmission setting.
RESUMO
Chemotherapy is generally effective as a non-targeted therapy in killing the majority of cells in a tumor; however, a small population of residual cells that are intrinsically resistant to such agents persist after chemotherapy, ultimately resulting in patient relapse. There is evidence that these cells within resistant tumors are cancer stem cells. A common mechanism of multidrug resistance used by residual tumor cells involves the expression of the ATP-binding cassette (ABC) transporters. Understanding the anticancer drug transport properties of these transporters, as well as their physiological functions, in addition to improved efforts to discover and characterize selective inhibitors, will lead to more effective therapeutics for oncology.
