Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro.

Enteroviruses, including Coxsackievirus B3 (CVB3), are pervasive pathogens that cause significant disease, including cardiomyopathies. Unfortunately, no treatments or vaccines are available for infected individuals. We identified the host polyamine pathway as a potential drug target, as inhibiting polyamine biosynthesis significantly reduces enterovirus replication in vitro and in vivo. Here, we show that CVB3 is sensitive to polyamine depletion through the polyamine analog diethylnorspermidine (DENSpm), which enhances polyamine catabolism through induction of polyamine acetylation. We demonstrate that CVB3 acquires resistance to DENSpm via mutation of the 2A protease, which enhances proteolytic activity in the presence of DENSpm. Resistance to DENSpm occurred via mutation of a non-catalytic site mutation and results in decreased fitness. These data demonstrate that potential for targeting polyamine catabolism as an antiviral target as well as highlight a potential mechanism of resistance.

An Operational Evaluation of 3 Methoprene Larvicide Formulations for Use Against Mosquitoes in Catch Basins.

Effectiveness in controlling mosquitoes in storm water catch basins in the North Shore Mosquito Abatement District (northeastern Cook County, Illinois) was determined for 3 formulations of methoprene-based larvicides (Altosid XR 150-day Briquets, Altosid 30-day Pellets, Altosid 30-day Granules) in 2017 using a pass/fail evaluation criterion, in which emergence of a single adult from pupae collected from the basin constituted a control failure. Over the course of the 16-week study, basins receiving the 150-day briquets were treated once and basins receiving the pellet and granular formulations were treated every 4 weeks, with the first treatment occurring during the last week of May. Untreated basins were also observed for comparison with the treated basins. Over the course of the study, adult mosquitoes emerged from pupae collected in 94.2% of the untreated basins that contained pupae. All of the formulations evaluated in the study demonstrated some degree of control compared with the untreated basins, with pupae successfully emerging as adults in 64.6%, 55.5%, and 21.8% of samples from 150-day briquet, 30-day tablet, and 30-day pellet-treated basins that contained pupae, respectively. Pellets reapplied every 28 days provided significantly more effective control than the other formulations. The simple pass/fail criterion for evaluating control effectiveness proved to be a useful procedure for comparing effectiveness to untreated basins and among treatments.

Standardized Operational Evaluations of Catch Basin Larvicides from Seven Mosquito Control Programs in the Midwestern United States During 2017.

During June to September 2017, 7 mosquito control programs in the midwestern United States evaluated a total of 9 catch basin larvicide formulations using similar protocols. Treated basins were monitored among study sites to observe when larvicides failed to control mosquitoes in 25% or more basins within a site. Overall, when monitoring occurred within the maximum label duration of the larvicides, sites treated with a single larvicide tablet or briquet surpassed the 25% fail threshold more often than pellet and granular larvicide formulations. In 438 of the study basins, the depth from sump bottom to catch basin lid was measured. In basins that were deeper than 5 ft (1.5 m), larvicides failed to control mosquitoes significantly more often than those 5 ft or shallower.

Reduced productivity of Culex pipiens and Cx. restuans (Diptera: Culicidae) mosquitoes in parking area catch basins in the northeast Chicago metropolitan area.

From June to September, 2016, 100 catch basins in eight parking areas were monitored weekly for the presence of mosquito pupae in the operational area of the North Shore Mosquito Abatement District (NSMAD) located just north of Chicago, IL, U.S.A. Weekly results from these basins were compared to weekly samples taken from residential street catch basins, the most common type of catch basin treated seasonally by the NSMAD with larvicides. Over the 17 study weeks, residential street basins had a mean rate of productivity (pupae per basin-visit) 12 times that of parking area catch basins. The two parking area sites with the highest mean rate of productivity were associated with county forest preserves. Productivity in both street and parking area basins was positively associated with the presence of three or more deciduous trees within 20 m of basins and if they were located directly adjacent to curbs. Alternatively, productivity was negatively associated with the proportion of impervious surface within 10 m of basins and weekly rainfall. Findings suggest that reduced catch basin larvicide applications may be appropriate in many parking area sites.