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.
Recognition of the significance of the boundary between ecological systems, often referred to as the ecotone, has a long history in the ecological sciences and in zoonotic disease research. More recent research in landscape ecology has produced an expanded view of ecotones and elaboration of their characteristics and functions in ecosystems. Parallel research on emerging infectious diseases (EIDs) and the causes of increased rates of pathogen transmission, spread, and adaptation suggests a correspondence between ecotonal processes and the ecological and evolutionary processes responsible for zoonotic and vector-borne emerging infections. A review of the literature suggests that ecotones play a role in a number of the most important EIDs. Yet these are the only diseases for which specific landscape ecological information exists in the literature or disease reports. However, the similar disease ecologies of these with about half of the approximately 130 zoonotic EIDs suggests ecotones, particularly their anthropogenic origination or modification, may be generally associated with ecotones and the global trend of increasing EIDs.
Of all countries in the Western Hemisphere, Brazil has the highest economic losses caused by dengue fever. We evaluated the cost-effectiveness of a novel system of vector surveillance and control, Monitoramento Inteligente da Dengue (Intelligent Dengue Monitoring System [MID]), which was implemented in 21 cities in Minas Gerais, Brazil. Traps for adult female mosquitoes were spaced at 300-m intervals throughout each city. In cities that used MID, vector control was conducted specifically at high-risk sites (indicated through daily updates by MID). In control cities, vector control proceeded according to guidelines of the Brazilian government. We estimated that MID prevented 27,191 cases of dengue fever and saved an average of $227 (median $58) per case prevented, which saved approximately $364,517 in direct costs (health care and vector control) and $7,138,940 in lost wages (societal effect) annually. MID was more effective in cities with stronger economies and more cost-effective in cities with higher levels of mosquito infestation.
Despite a safe and effective vaccine, there are approximately 200,000 cases, including 30,000 deaths, due to yellow fever virus (YFV) each year, of which 90% are in Africa. The natural history of YFV has been well described, especially in West Africa, but in East Africa yellow fever (YF) remains characterised by unpredictable focal periodicity and a precarious potential for large epidemics. Recent outbreaks of YF in Kenya (1992-1993) and Sudan (2003 and 2005) are important because each of these outbreaks have involved the re-emergence of a YFV genotype (East Africa) that remained undetected for nearly 40 years and was previously unconfirmed in a clinically apparent outbreak. In addition, unlike West Africa and South America, YF has yet to emerge in urban areas of East Africa and be vectored by Aedes (Stegomyia) aegypti. This is a significant public health concern in a region where the majority of the population remains unvaccinated. This review describes historical findings, highlights a number of disease indicators, and provides clarification regarding the natural history, recent emergence and future risk of YF in East Africa.
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