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Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

Major dengue epidemics have been observed in the Indian subcontinent since the 1980s and have occurred with increased hospitalizations and mortality. In 2011, the first major epidemic of dengue occurred in Lahore, the second largest city in Pakistan, and resulted in 21,685 confirmed cases and 350 deaths. To investigate the possible viral causes for the increased epidemic activity, we determined the predominant serotype and characterized the viruses genetically. Of 50 patients carefully selected as probable dengue fever or dengue hemorrhagic fever, 34 were positive by virologic testing (i.e. PCR and/or virus isolation). DENV-2 was detected in 32 patients and DENV-1 in two. A total of 24 partial and three full DENV genomes were sequenced. Phylogenetic analyses of the capsid (C), pre-membrane (prM), and envelope genes comprising 2500 nucleotides in length indicated that all DENV-2 isolates in Pakistan since 2007 form a monophyletic lineage that is endemic in the country. These viruses were all of the cosmopolitan genotype (IV) and most closely related to viruses isolated in India and Sri Lanka in the past two decades. Phylogenetic analyses of data currently available in GenBank suggest that the Cosmopolitan genotype has diverged into two geographically distinct sub-lineages: sub-lineage IV-a has only been observed in Southeast Asia, China and Oceania, while IV-b is prevalent in the Indian subcontinent. These results highlight the increased diversity of dengue viruses as they spread geographically within the region.

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira . We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira . In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus . A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L . borgpetersenii and 3 were L . kirschneri ; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans . Serotyping of L . borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

Given the limited potable water supply in the U.S. Virgin Islands, most residents use cisterns to collect rainwater and store it for their daily needs. A survey conducted in 2019 found that 45.7% of the cisterns contained mosquitoes, and 83.3% of the mosquitoes collected were Aedes aegypti , suggesting an important role as mosquito larval development sites. A subsequent entomological survey was designed to determine the importance of cisterns in producing Ae. aegypti mosquitoes and to understand the cistern factors and characteristics that influence productivity. Three floating funnel traps were installed inside each sampled cistern to collect immature mosquitoes, and exit traps were installed on the intake spouts and overflow pipes, when possible, to collect adult mosquitoes. Physical and chemical characteristics were also recorded. Yard and outdoor patio inspections were conducted at participating households to identify other types of containers with immature mosquitoes. A total of 1,858 households were visited, of which 24% granted access to their cisterns for this study. Of these, 76% of cisterns met protocol criteria, which resulted in 342 cisterns being sampled. Approximately half of the cisterns surveyed were positive for immature mosquitoes. A higher percentage was observed on the St. Thomas and St. John islands (STT District, 57.3%) than St. Croix (STX District, 40.9%). Most immature mosquitoes collected were Ae. aegypti (89.2%), followed by Culex spp . (1.3%), and Ae. mediovittatus (0.38%). Pupal surveys revealed that cisterns were the second highest contributor to the production of Ae. aegypti pupae, with 16.9% of the pupae collected from cisterns. However, this number might be underestimated given sampling limitations. Buckets were the highest Ae. aegypti pupal producer with 47.3%. On average, 5.8% of the exit traps installed on cisterns captured adult mosquitoes, with higher rates of capture on the STT district than on the STX (6.4% versus 5.3%, respectively). Most adult mosquitoes collected (90.7%) were identified as Ae. aegypti, while the other 9.2% were Culex spp . We can conclude that cisterns are important larval development sites for Ae. aegypti and vector management strategies must be developed to reduce their impact.

Dengue and chikungunya are global re-emerging mosquito-borne diseases. In Singapore, sustained vector control coupled with household improvements reduced domestic mosquito populations for the past 45 years, particularly the primary vector Aedes aegypti. However, while disease incidence was low for the first 30 years following vector control implementation, outbreaks have re-emerged in the past 15 years. Epidemiological observations point to the importance of peridomestic infection in areas not targeted by control programs. We investigated the role of vectors in peri-domestic areas. We carried out entomological surveys to identify the Aedes species present in vegetated sites in highly populated areas and determine whether mosquitoes were present in open-air areas frequented by people. We compared vector competence of Aedes albopictus and Aedes malayensis with Ae. aegypti after oral infection with sympatric dengue serotype 2 and chikungunya viruses. Mosquito saliva was tested for the presence of infectious virus particles as a surrogate for transmission following oral infection. We identified Aedes albopictus and Aedes malayensis throughout Singapore and quantified their presence in forested and opened grassy areas. Both Ae. albopictus and Ae. malayensis can occupy sylvatic niches and were highly susceptible to both arboviruses. A majority of saliva of infected Ae. malayensis contained infectious particles for both viruses. Our study reveals the prevalence of competent vectors in peri-domestic areas, including Ae. malayensis for which we established the vector status. Epidemics can be driven by infection foci, which are epidemiologically enhanced in the context of low herd immunity, selective pressure on arbovirus transmission and the presence of infectious asymptomatic persons, all these conditions being present in Singapore. Learning from Singapore's vector control success that reduced domestic vector populations, but has not sustainably reduced arboviral incidence, we suggest including peri-domestic vectors in the scope of vector management.

Additive manufacturing of metals is limited by a fundamental tradeoff between deposition rates and manufacturability of fine-scale features. To overcome this problem, a laser-ablated bound metal deposition (laBMD) process is demonstrated in which 3D-printed green-state bound metal deposition (BMD) parts are post-processed via laser ablation prior to conventional BMD debinding and sintering. The laBMD process is experimentally characterized via a full-factorial design of experiments to determine the effect of five factors—number of laser passes (one pass, three passes), laser power (25%, 75%), scanning speed (50%, 100%), direction of laser travel (perpendicular, parallel), and laser resolution (600 dpi, 1200 dpi)—on as-sintered ablated depth, surface roughness, width, and angle between ablated and non-ablated regions. The as-sintered ablation depth/pass ranged from 3 to 122 µm/pass, the ablated surface roughness ranged from 3 to 79 µm, the angle between ablated and non-ablated regions ranged from 1° to 68°, and ablated bottom widths ranged from 729 to 1254 µm. This study provides novel insights into as-manufactured ablated geometries and surface finishes produced via laser ablation of polymer–metallic composites. The ability to inexpensively and accurately manufacture fine-scale features with tailorable geometric tolerances and surface finishes is important to a variety of applications, such as manufacturing molds for microfluidic devices.

We reconstructed the 2016-2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic's origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.

Most residences in the United States Virgin Islands (USVI) rely on household rainwater-catchment systems and subterranean cisterns for long-term water storage that may provide suitable habitats for mosquitoes of public health relevance. We conducted a household cistern survey ( n = 164) on the islands of St. Croix, St. John, and St. Thomas in 2019. The survey revealed that 45.7% (95% CI: 38.3–53.4%) of cisterns contained mosquitoes (adult and/or immature mosquitoes). Aedes aegypti , a vector of chikungunya, dengue, and Zika viruses in the USVI, was found in 27.4% (95% CI: 21.2–34.7%) of cisterns and accounted for 83.3% of the total mosquitoes identified in the study. The odds of detecting mosquitoes in a cistern were 5.45 times higher at locations where the residents reported that they had observed adult mosquitoes coming out of their cisterns (95% CI: 2.25–14.21), suggesting that vector control personnel should consider resident complaints about mosquitoes in their cistern as valid and likely reliable self-assessments. Resident mosquito management practices in cisterns did not correspond with decreased odds of mosquito detection. We conclude that cisterns in the USVI commonly provide habitat for immature and adult Ae. aegypti , which may decrease the effectiveness of area-wide mosquito control strategies. Additional studies are necessary to evaluate the importance of these cisterns as they relate to mosquito production and arbovirus transmission risk, and to assess physical and chemical control methods.

The Aedes aegypti mosquito first invaded the Americas about 500 years ago and today is a widely distributed invasive species and the primary vector for viruses causing dengue, chikungunya, Zika, and yellow fever. Here, we test the hypothesis that the North American colonization by Ae. aegypti occurred via a series of founder events. We present findings on genetic diversity, structure, and demographic history using data from 70 Ae. aegypti populations in North America that were genotyped at 12 microsatellite loci and/or ~20,000 single nucleotide polymorphisms, the largest genetic study of the region to date. We find evidence consistent with colonization driven by serial founder effect (SFE), with Florida as the putative source for a series of westward invasions. This scenario was supported by (1) a decrease in the genetic diversity of Ae. aegypti populations moving west, (2) a correlation between pairwise genetic and geographic distances, and (3) demographic analysis based on allele frequencies. A few Ae. aegypti populations on the west coast do not follow the general trend, likely due to a recent and distinct invasion history. We argue that SFE provides a helpful albeit simplified model for the movement of Ae. aegypti across North America, with outlier populations warranting further investigation. We find support for the hypothesis that the North American colonization by the yellow fever mosquito (Aedes aegypti) occurred via a series of founder events with Florida as the putative source. We present findings on genetic diversity, structure, and demographic history using data from 70 Ae. aegypti populations in North America that were genotyped at 12 microsatellite loci and/or ~20,000 single nucleotide polymorphisms, the largest genetic study of the region to date.