West Nile virus in India: An update on its genetic lineages.

West Nile virus (WNV) is a rapidly spreading mosquito-transmitted zoonotic flavivirus. Mosquitoes belonging to the genus Culex are incriminated as the principal vectors of the virus, which causes West Nile fever (WNF) in humans. Manifestations of WNF include a mild, self-limiting, flu-like illness, which in severe cases (rare) may progress to encephalitis, resulting in life-threatening consequences. WNV is geographically distributed worldwide, covering Africa, the Americas, Europe, and Asia (except Antarctica). The virus exists in a bird-mosquito transmission cycle in nature, with humans and horses as incidental/accidental hosts. The virus can infect a large variety of hosts worldwide, i.e., about 300 birds and around 70 different mosquito species belonging to several genera. For a long time, it was believed that WNV was not highly virulent and caused only mild infection globally. However, the recent frequent and increasing incidence of clinically severe WNV infections, such as encephalitis in humans and horses with significant mortality, has been reported in the Americas, Europe, and several East Asian countries. The emergence of lineage 2 strains endemic to Africa, with epidemic potential in humans and horses in Europe, is considered a serious global health concern. Although WNV is known to circulate in India since 1952, its re-emergence with severe neuro-invasive pathogenic potential in humans in Assam, Kerala, West Bengal and Tamil Nadu states signals urgent efforts to understand the dynamics of circulating strains with regard to its vector, hosts, and environment. This could be done by prioritizing "One Health" approach for developing effective preventive and control strategies. In view of the global interest, we present an overview of the circulating genetic lineages of WNV in India in comparison with the global scenario. In addition, we stress on holistic approaches of "One Health" strategy as the current need of the hour for designing effective preventive and control strategies in the country.

Process evaluation of integrated West Nile virus surveillance in northern Italy: an example of a One Health approach in public health policy.

West Nile virus (WNV) is endemic in the Po valley area in northern Italy. Regional health authorities have implemented integrated WNV surveillance following a One Health approach, based on collaboration between human, animal and environmental health institutions. We evaluated this integrated WNV surveillance system in Emilia-Romagna, Lombardy and Piedmont regions by means of a process evaluation. We examined the system's implementation fidelity, dose delivered and received, reach, and we identified strengths and weaknesses in the system. Qualitative and semi-quantitative data were obtained from three regional focus groups. Data were discussed in a follow up focus group, where participants suggested recommendations for improving the surveillance system. Inter-institutional and interdisciplinary integration and the creation of a 'community of practice' were identified as key elements for effective surveillance. We identified differences in the degree of interdisciplinary integration in the three regions, likely due to different epidemiological situations and years of experience in surveillance implementation. Greater collaboration and sharing of information, public engagement and economic assessments of the integrated surveillance approach would facilitate its social recognition and guarantee its sustainability through dedicated funding. We demonstrate that a transdisciplinary research approach based on process evaluation has value for designing and fine-tuning integrated health surveillance systems.

Combined effects of energy development and disease on greater sage-grouse.

Species of conservation concern are increasingly threatened by multiple, anthropogenic stressors which are outside their evolutionary experience. Greater sage-grouse are highly susceptible to the impacts of two such stressors: oil and gas (energy) development and West Nile virus (WNv). However, the combined effects of these stressors and their potential interactions have not been quantified. We used lek (breeding ground) counts across a landscape encompassing extensive local and regional variation in the intensity of energy development to quantify the effects of energy development on lek counts, in years with widespread WNv outbreaks and in years without widespread outbreaks. We then predicted the effects of well density and WNv outbreak years on sage-grouse in northeast Wyoming. Absent an outbreak year, drilling an undeveloped landscape to a high permitting level (3.1 wells/km²) resulted in a 61% reduction in the total number of males counted in northeast Wyoming (total count). This was similar in magnitude to the 55% total count reduction that resulted from an outbreak year alone. However, energy-associated reductions in the total count resulted from a decrease in the mean count at active leks, whereas outbreak-associated reductions resulted from a near doubling of the lek inactivity rate (proportion of leks with a last count = 0). Lek inactivity quadrupled when 3.1 wells/km² was combined with an outbreak year, compared to no energy development and no outbreak. Conservation measures should maintain sagebrush landscapes large and intact enough so that leks are not chronically reduced in size due to energy development, and therefore vulnerable to becoming inactive due to additional stressors.

Public health and vector-borne diseases - a new concept for risk governance.

Public Health is defined as an interdisciplinary multilevel approach that deals with questions of preventing diseases at the population level. In this context, this paper focuses on vector-borne diseases as an important threat with an increasing impact on human and animal health. Emphasis is laid on an integrated health approach ('One-Health' initiative) as it recognizes the interrelated nature of both human and animal health. The importance of vector-borne diseases to new and emerging diseases in Europe was demonstrated, for example, by the recent outbreak of West Nile virus infections in Greece, Northern Italy and Hungary; the spread of Crimean-Congo haemorrhagic fever virus across Turkey, south-western countries of the former USSR and the Balkans; the dramatic increase in hantavirus infections in Germany in 2012; and the dengue virus outbreak in Portugal in the same year. This paper provides a systematic approach for the analysis, assessment and governance of emerging health risks attributed to vector-borne diseases by using a holistic approach developed by the International Risk Governance Council (IRGC), called the 'IRGC Risk Governance Framework'. It can be used by decision-makers and general Public Health authorities in order to evaluate the situation regarding any specific pathogen or Public Health risk and to decide if additional measures should be implemented.

West Nile Virus: is a vaccine needed?

West Nile virus (WNV) is a neurotropic Flavivirus that was associated with sporadic outbreaks of meningoencephalitis in Africa and the Middle East until 1999, when a more virulent strain emerged in the US that caused thousands of infections among humans and horses, with reported fatality rates between 10 and 50%. Although the epidemiology of WNV is changing into a more endemic pattern in the US, and the incidence of neuroinvasive disease is decreasing, the long-term effects of resolved WNV infections in humans, characterized as persistent movement disorders and various functional disabilities, are a significant cause of morbidity. In addition, the horse industry is also negatively impacted by WNV infections, resulting in significant economic losses. Together with the fact that WNV is a potential bioterrorism agent, these factors suggest that there is a need for the development of a safe and effective vaccine against WNV. The increased understanding of WNV pathogenesis and correlates of protection enables the rational design of such a vaccine. Several experimental vaccines have been tested in preclinical models and some have undergone clinical trials. The challenges related to the development of cheaper, safer and more effective vaccines for use in both humans and horses are likely to be overcome by new technological developments in the field of vaccinology.

Adaptation of West Nile virus replicons to cells in culture and use of replicon-bearing cells to probe antiviral action.

Flaviviruses are emerging threats to public health worldwide. Recently, one flavivirus, West Nile virus (WNV), has caused the largest epidemic of viral encephalitis in US history. Like other flaviviruses, WNV is thought to cause a persistent infection in insect cells, but an acute cytopathic infection of mammalian cells. To study adaptation of WNV to persistently replicate in cell culture and generate a system capable of detecting antiviral compounds in the absence of live virus, we generated subgenomic replicons of WNV and adapted these to persistently replicate in mammalian cells. Here we report that adaptation of these replicons to cell culture results in a reduction of genome copy number, and demonstrate that hamster, monkey, and human cells that stably carry the replicons can be used as surrogates to detect the activity of anti-WNV compounds. Additionally, we have used these cells to investigate the interaction of WNV genomes with interferon (IFN). These studies demonstrated that IFN can cure cells of replicons and that replicon-bearing cells display lower responses to IFN than their IFN-cured derivatives.

West Nile virus: success of public health response underlines failure of the system.

The West Nile virus outbreak in 1999 demonstrated the country's capacity to meet an emerging public health threat. However, while the tracking and monitoring efforts that were put into place by 2000 were impressive, the response to the West Nile virus underscores a fundamental deficiency in the capacity of public health regarding the nation's environmental health efforts. Chronic diseases such as asthma, neurological diseases, and birth defects and their potential links to environmental factors are not being adequately tracked and monitored. New public health infrastructure resources are required.

Prospects for development of a vaccine against the West Nile virus.

Vaccination provides the ultimate measure for personal protection against West Nile disease. The development of a West Nile vaccine for humans is justified by the uncertainty surrounding the size and frequency of future epidemics. At least two companies (Acambis Inc. and Baxter/immuno) have initiated research and development on human vaccines. West Nile encephalitis has also emerged as a significant problem for the equine industry. One major veterinary vaccine manufacturer (Ft. Dodge) is developing formalin-inactivated and naked DNA vaccines. The advantages and disadvantages of formalin-inactivated whole virion vaccines, Japanese encephalitis vaccine for cross-protection, naked DNA, and live attenuated vaccines are described. A novel technology platform for live, attenuated recombinant vaccines (ChimeriVax) represents a promising approach for rapid development of a West Nile vaccine. This technology uses yellow fever 17D as a live vector for envelope genes of the West Nile virus. Infectious clone technology is used to replace the genes encoding the prM and E structural proteins of yellow fever 17D vaccine virus with the corresponding genes of West Nile virus. The resulting virion has the protein coat of West Nile, containing all antigenic determinants for neutralization and one or more epitopes for cytotoxic T lymphocytes. The genes encoding the nucleocapsid protein, nonstructural proteins, and untranslated terminal regions responsible for replication remain those of the original yellow fever 17D virus. The chimeric virus replicates in the host like yellow fever 17D but immunizes specifically against West Nile virus.