Medical entomology: changes in the spectrum of mosquito-borne disease in Australia and other vector threats and risks, 1972–2004

Abstract   Our paper presents an assessment of research and operational development in relation to medically important mosquito-borne disease, mainly the arboviruses Ross River, Barmah Forest, Murray Valley encephalitis, Japanese encephalitis, Kunjin and dengue, but also with respect to malaria. Since 1972, there have been considerable gains in research output, organisational structure, communication, surveillance including quarantine inspection and operational control. This has been due to the 1974 epidemic of Murray Valley encephalitis virus extending into temperate Australia, increasing occurrence of Ross River and the dengue viruses, the discovery of Barmah Forest virus as a disease entity in 1988, and the introduction of Japanese encephalitis in 1995. Because many of the outputs involve methodologies of global import, this has resulted in an unprecedented upsurge in publications of international standard.     

A FRET-based assay for the discovery of West Nile Virus NS2B-NS3 protease inhibitors

The West Nile Virus (WNV) has been a worldwide epidemic since the early 1990s. Currently there are no therapeutic treatments for WNV infections. One particular avenue of treatment is inhibition of the NS2B-NS3 protease, an enzyme that is crucial for WNV replication. In our effort to increase the number of NS2B-NS3 protease inhibitors, we report a novel FRET-based high throughput assay for the discovery of WNV NS2B-NS3 protease inhibitors. For this assay, a FRET-based peptide substrate was synthesized and kinetically characterized with the NS2B-NS3 protease. The new substrate exhibits a K_m of 3.35 ± 0.31 μM, a k_cat of 0.0717 ± 0.0016 s^?1 and a k_cat/K_m of 21,400 ± 2000 M^?1 s^?1.     

Seasonality and Outbreaks in West Nile Virus Infection

In this paper we analyze the impact of seasonal variations on the dynamics of West Nile Virus infection. We are interested in the generation of new epidemic peaks starting from an endemic state. In many cases, the oscillations generated by seasonality in the dynamics of the infection are too small to be observable. The interplay of this seasonality with the epidemic oscillations can generate new outbreaks starting from the endemic state through a mechanism of parametric resonance. Using experimental data we present specific cases where this phenomenon is numerically observed.     

野生鸟类传染性疾病研究进展

由于具有独特的飞行能力和极强的地理扩散能力,鸟类活动为某些传染性疾病的快速传播和扩散带来了潜在风险.自20世纪以来,以禽霍乱、禽波特淋菌病、西尼罗河热、禽流感等为代表的鸟类疾病频繁暴发,导致为数众多的野生鸟类、家禽甚至人类死亡,给社会造成巨大的经济损失.因此,有关鸟类传染性疾病的研究已引起了国内外学者的广泛关注.从鸟类传染性疾病的生态学特征、疾病对鸟类与人类社会的影响、鸟类对疾病的传播、鸟类疾病的监测、预警和防控等方面对野生鸟类的传染性疾病研究进展进行了综述.不同疾病导致的鸟类死亡量、易感物种数量、暴发频率和地理扩散等特征差异显著.20世纪以来,疾病已成为全球生物多样性的七大威胁因子之一.疾病可能造成鸟类大量死亡,从而对鸟类种群,特别是濒危鸟类种群造成严重影响.其中,人畜共患病还会导致家禽家畜甚至人类的死亡,从而对社会产生严重的影响.野生鸟类作为多种疾病传播的媒介,其移动和迁徙可能会导致疾病的传播与扩散.开展全面的监测活动和建立疾病预警体系,对于疾病的防控具有重要意义.     

Spatial spreading of West Nile Virus described by traveling waves

In this work, we propose a spatial model to analyze the West Nile Virus propagation across the USA, from east to west. West Nile Virus is an arthropod-borne flavivirus that appeared for the first time in New York City in the summer of 1999 and then spread prolifically among birds. Mammals, such as humans and horses, do not develop sufficiently high bloodstream titers to play a significant role in the transmission, which is the reason to consider the mosquito-bird cycle. The model aims to study this propagation based on a system of partial differential reaction-diffusion equations taking the mosquito and the avian populations into account. Diffusion and advection movements are allowed for both populations, being greater in the avian than in the mosquito population. The traveling wave solutions of the model are studied to determine the speed of disease dissemination. This wave speed is obtained as a function of the model's parameters, in order to assess the control strategies. The propagation of West Nile Virus from New York City to California state is established as a consequence of the diffusion and advection movements of birds. Mosquito movements do not play an important role in the disease dissemination, while bird advection becomes an important factor for lower mosquito biting rates.     

A Novel Imidazole Nucleoside Containing a Diaminodihydro-S-triazine as a Substituent: Inhibitory Activity Against the West Nile Virus NTPase/Helicase

The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2′-deoxy-β-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2′-deoxy-β-D-erythropentofuranosyl)-5-(2,4-diamino-3,6-dihydro-1,3,5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/ helicase with an IC ₅₀ of 3-10 μg/mL.