Genetic Characterization of Highly Pathogenic Avian Influenza A(H5N8) Virus in Pakistani Live Bird Markets Reveals Rapid Diversification of Clade 2.3.4.4b Viruses.

The highly pathogenic (HPAI) avian influenza A(H5N1) viruses have undergone reassortment with multiple non-N1-subtype neuraminidase genes since 2008, leading to the emergence of H5Nx viruses. H5Nx viruses established themselves quickly in birds and disseminated from China to Africa, the Middle East, Europe and North America. Multiple genetic clades have successively evolved through frequent mutations and reassortment, posing a continuous threat to domestic poultry and causing substantial economic losses. Live bird markets are recognized as major sources of avian-to-human infection and for the emergence of zoonotic influenza. In Pakistan, the A(H5N1) virus was first reported in domestic birds in 2007; however, avian influenza surveillance is limited and there is a lack of knowledge on the evolution and transmission of the A(H5) virus in the country. We collected oropharyngeal swabs from domestic poultry and environmental samples from six different live bird markets during 2018-2019. We detected and sequenced HPAI A(H5N8) viruses from two chickens, one quail and one environmental sample in two markets. Temporal phylogenetics indicated that all novel HPAI A(H5N8) viruses belonged to clade 2.3.4.4b, with all eight genes of Pakistan A(H5N8) viruses most closely related to 2017 Saudi Arabia A(H5N8) viruses, which were likely introduced via cross-border transmission from neighboring regions approximately three months prior to virus detection into domestic poultry. Our data further revealed that clade 2.3.4.4b viruses underwent rapid lineage expansion in 2017 and acquired significant amino acid mutations, including mutations associated with increased haemagglutinin affinity to human α-2,6 receptors, prior to the first human A(H5N8) infection in Russian poultry workers in 2020. These results highlight the need for systematic avian influenza surveillance in live bird markets in Pakistan to monitor for potential A(H5Nx) variants that may arise from poultry populations.

Avian influenza at animal-human interface: One-health challenge in live poultry retail stalls of Chakwal, Pakistan.

BACKGROUND: Live poultry retail stalls (LPRSs) are believed to be the source of human infection with avian influenza viruses (AIVs); however, little is known about epidemiology of these viruses in LPRSs of Pakistan. OBJECTIVES: The current study was conducted to estimate the virological and serological prevalence of AIVs in humans and poultry and associated risk factors among seropositive butchers. METHODS: A field survey of LPRSs of Chakwal District was conducted between December 2015 and March 2016. In total, 322 samples (sera = 161 and throat swab = 161) from butchers and 130 pooled oropharyngeal swabs and 100 sera from birds were collected. Baseline sera (n = 100) from general population were also tested. Data were collected by structured questionnaires. Sera were tested by hemagglutination inhibition (HI) test further confirmed by micro-neutralization test (MN). Swabs were processed by real-time RT-PCR. Logistic regression analyses were conducted to identify risk factors. RESULTS: In butchers, 15.5% sera were positive for antibodies against H9 virus using a cutoff of ≥40 in HI titer; 6% sera from general population were positive for H9. Seroprevalence in poultry was 89%, and only 2.30% swabs were positive for H9. Presence of another LPRS nearby and the number of cages in the stall were risk factors (OR > 1) for H9 seroprevalence in butchers. CONCLUSIONS: This study provides evidence of co-circulation of H9 virus in poultry and exposure of butchers in the LPRSs, which poses a continued threat to public health. We suggest regular surveillance of AIVs in occupationally exposed butchers and birds in LPRSs.

Disentangling the role of Africa in the global spread of H5 highly pathogenic avian influenza.

The role of Africa in the dynamics of the global spread of a zoonotic and economically-important virus, such as the highly pathogenic avian influenza (HPAI) H5Nx of the Gs/GD lineage, remains unexplored. Here we characterise the spatiotemporal patterns of virus diffusion during three HPAI H5Nx intercontinental epidemic waves and demonstrate that Africa mainly acted as an ecological sink of the HPAI H5Nx viruses. A joint analysis of host dynamics and continuous spatial diffusion indicates that poultry trade as well as wild bird migrations have contributed to the virus spreading into Africa, with West Africa acting as a crucial hotspot for virus introduction and dissemination into the continent. We demonstrate varying paths of avian influenza incursions into Africa as well as virus spread within Africa over time, which reveal that virus expansion is a complex phenomenon, shaped by an intricate interplay between avian host ecology, virus characteristics and environmental variables.

Chinese poultry farmers' decision-making for avian influenza prevention: a qualitative analysis.

Poultry farmers faced dual risk when mutant avian influenza (AI) virus showed the zoonotic characteristics. A/H5N1 and A/H7N9 were two dominant AI virus strains that have captured the attention of the public over the years for they have been reported to bring about greater loss to poultry and human, respectively. Previous studies mainly used quantitative methods investigating either the means that poultry farmers adopted for protecting their poultry against A/H5N1 infection or the poultry farmers' self-protective behaviours against A/H7N9 infection. We sought insights into the underlying factors influencing Chinese poultry farmers' protective behaviours in response to the dual risk of AI by a qualitative way. Semi-structured in-depth interviews were conducted with 25 Chinese chicken farmers recruited by purposive sampling between November 2016 and May 2017, the peak season of AI. All interviews were audio-taped, transcribed and analysed using a grounded theory approach. From participants' experiences, we revealed five main themes: Measures adopted for protecting poultry and farmers, Emotional response to the AI epidemic, Perceived risk of AI, Perceived effectiveness of the preventive measures adopted and Perceived self-efficacy to take preventive measures. The information of AI outbreak directly triggered Chinese chicken farmers' emotional response and thereafter preventive actions. Compared to the perceived risk of poultry infection with A/H5N1 which mainly connected to economic loss, participants perceived much lower risk of human infection with A/H7N9. AI epidemic information played a key role triggering poultry farmers' response behaviours. Chinese poultry farmers weighted more attention on the risk of poultry infection which was highly associated with economic losses. The government should build and improve an early AI warning and information transmission network to poultry farmers. Further reinforcement of related self-protective and preventive knowledge training towards poultry farmers is necessary.

National surveillance and control costs for highly pathogenic avian influenza H5N1 in poultry: A benefit-cost assessment for a developing economy, Nigeria.

We conducted benefit-cost analysis of outbreak and surveillance costs for HPAI H5N1in poultry in Nigeria. Poultry's death directly cost US$ 939,734.0 due to outbreaks. The integrated disease surveillance and response originally created for comprehensive surveillance and laboratory investigation of human diseases was adapted for HPAI H5N1 in poultry. Input data were obtained from the field, government documents and repositories and peer-reviewed publications. Actual/forecasted bird numbers lost were integrated into a financial model and estimates of losses were calculated. Costs of surveillance as alternative intervention were determined based on previous outbreak control costs and outputs were generated in SurvCost® with sensitivity analyses for different scenarios. Uncontrolled outbreaks will lead to loss of over US$ 2.2 billion annually in Nigeria with 47.8% of the losses coming from eggs. The annual cost of all animal related health activities was

Spotlight on avian pathology: red mite, a serious emergent problem in layer hens.

Dermanyssus gallinae, the poultry red mite, is currently the most important ectoparasite of the egg laying industry worldwide with an expanding global prevalence. As a blood-feeder, it causes anaemia and severe welfare issues to the hens and it is a major cause of economic losses. It is also a vector for Salmonella species, avian influenza and potentially for other vector-borne pathogens. Paradoxically, there is a notable lack of funding for research into poultry red mite and an urgent need for effective and safe control strategies, sustainable therapies, prophylactics and integrated pest management.

Economic impacts of avian influenza outbreaks in Kerala, India.

This study assessed the short-run impact to poultry farmers, duck hatcheries, control costs, compensation paid to stakeholders (transfer payments) and market reactions on own and substitute product prices and backwater tourism (boat operators) due to avian influenza (AI) outbreaks in Kuttanad region of Kerala, India, during 2014. The primary data from 91 poultry farms (duck farms, broiler chicken and backyard poultry), four hatcheries and 90 backwater boat owners were collected through pre-tested schedules. The secondary data on transfer payments and expenditure incurred to control AI were collected from developmental departments and were analysed. The estimated loss (culling live birds, eggs and feed destruction) per duck farm was USD 9,181, USD 3,889 and USD 156 in case of commercial farms reared for meat, dual-purpose and backyard farms, respectively. The loss incurred by small-scale broiler and backyard poultry farms was USD 453 and USD 40, respectively. The loss incurred by large and small duck hatcheries was USD 11,963 and USD 5,790, respectively, due to culling of hatchlings, young birds and destroying eggs. The government invested USD 744,890 to contain the disease spread through massive culling, surveillance and monitoring of poultry and humans due to zoonotic nature of the disease. A sharp market reaction on own and substitute product prices and eight weeks' time lag in price recovery was observed. The consequential impact on tourism especially for the backwater boat operators amounted to a loss of USD 2,280/boat due to fall in tourist inflow. Since, control measures are post-incidence, it is necessary to adopt appropriate preventive bio-security measures at the farm level besides periodical screening of domestic birds in migratory birds' flyway locations like Kuttanad to reduce the AI burden on various stakeholders including government.

Animal health economics: an aid to decisionmaking on animal health interventions - case studies in the United States of America.

For animal disease events the outcomes and consequences often remain unclear or uncertain, including the expected changes in benefits (e.g. profit to firms, prices to consumers) and in costs (e.g. response, clean-up). Moreover, the measurement of changes in benefits and costs across alternative interventions used to control animal disease events may be inexact. For instance, the economic consequences of alternative vaccination strategies to mitigate a disease can vary in magnitude due to trade embargoes and other factors. The authors discuss the economic measurement of animal disease outbreaks and interventions and how measurement is used in private and public decision-making. Two illustrative case studies in the United States of America are provided: a hypothetical outbreak of foot and mouth disease in cattle, and the 2014-2015 outbreak of highly pathogenic avian influenza in poultry.

Lors d'un événement sanitaire, les résultats et les conséquences d'une intervention sont souvent incertains ou imprécis, y compris pour ce qui concerne l'évolution attendue des bénéfices (par ex. le profit pour les entreprises ou le prix payé par le consommateur) et des coûts (par ex. le coût de la réponse ou de l'assainissement). De plus, la mesure de l'évolution des bénéfices et des coûts suivant les différentes interventions utilisées pour lutter contre les maladies animales peut s'avérer inexacte. Par exemple, les conséquences économiques de différentes stratégies de vaccination visant à atténuer l'impact d'une maladie peuvent varier en ordre de grandeur du fait des restrictions imposées au commerce suite à la vaccination, ou d'autres facteurs. Les auteurs examinent l'évaluation économique des foyers de maladies animales et des interventions sanitaires ainsi que l'utilisation de ces évaluations dans les prises de décision du secteur privé et public. L'analyse est illustrée par deux études de cas aux États- Unis d'Amérique : l'hypothèse d'un foyer de fièvre aphteuse survenant dans la population bovine, et le foyer d'influenza aviaire hautement pathogène survenu en 2014­2015 chez les volailles.

A menudo los resultados o efectos de ciertos episodios zoosanitarios quedan poco claros o generan incertidumbre, por ejemplo sobre el modo en que en principio modifican los beneficios (réditos para las empresas, precios para el consumidor) y los costos (p.ej. de respuesta o de saneamiento de la explotación). Además, la medición de los cambios que experimenten los costos y beneficios a resultas de distintas intervenciones posibles para combatir un episodio zoosanitario puede resultar inexacta. Por ejemplo: las consecuencias económicas de estrategias alternativas de vacunación para mitigar una enfermedad pueden ser de magnitud variable dependiendo de la existencia de embargos comerciales u otros factores. Los autores examinan la cuantificación económica de los brotes de enfermedades animales y las intervenciones para combatirlos y explican cómo se utilizan esas mediciones para tomar decisiones en los sectores público y privado, ofreciendo como ejemplo casos situados en los Estados Unidos de América: un brote hipotético de fiebre aftosa en el ganado vacuno y el brote de influenza aviar altamente patógena que en 2014 y 2015 afectó a las aves de corral.

Chinese farmers' willingness to accept compensation to practice safe disposal of HPAI infected chicken.

Highly Pathogenic Avian Influenza (HPAI) is a high morbidity and mortality zoonotic disease, which threatens poultry and human health. An outbreak of disease in China requires strict slaughter and disposal of all chickens within a three-kilometer radius, incurring large private costs for farmers and encouraging black market transactions. A stated preference survey of 331 farmers across six provinces in China was conducted in 2015, in order to measure the responsiveness of farmers to accept various compensation prices for safely disposing of HPAI infected chicken. Findings suggest that about 25% and 40% of farmers in South and North China respectively would not adopt safe disposal at the current compensation price (10 yuan/bird) offered by the government. However, 80% of farmers would adopt safe disposal if the compensation price increased to 14.1 yuan in South China and 18.9 yuan in North China. The adoption of safe disposal by farmers was positively and significantly influenced by compensation price (p=0.000) and regular contact with epidemic prevention staff (p=0.094). However, adoption was negatively and significantly influenced by net farm income (p=0.100) and chicken production income percentage (p=0.014). Although half of (51%) of farmers were willing to receive zero compensation, a reasonable compensation scheme along with strengthened supervision, may be considered the most effective strategy to encourage safe disposal of HPAI infected chicken and reduce the risks associated with black market transactions.

Assessment of China's H5N1 routine vaccination strategy.

In this study, a simulation model was used to assess the epidemiological and economic impacts of the routine vaccination strategy for H5N1 in China at the national level. The results of the simulation show that a routine vaccination strategy at the national level could have a substantial impact on decreasing H5N1 outbreaks; it could therefore markedly reduce the severity and duration of an H5N1 epidemic at the national level in China. Under a routine vaccination programme, when a flock is infected, the number of depopulated birds could be reduced by approximately 91%, the outbreak duration could be reduced by one-fourth, and the probability of an H5N1 outbreak could be reduced to 51.5%. Although the use of vaccination has obvious benefits, if indirect costs were not considered, the mean direct cost of simulated disease control without vaccination was only 1.36% of the cost of the routine vaccination strategy, and this former approach would have saved 57 billion yuan for all poultry in China from 2004 to 2012. Traditional H5N1 control strategies with culling programmes at the national level represented a better choice for China.

Safe application of regionalization for trade in poultry and poultry products during highly pathogenic avian influenza outbreaks in the USA.

The 2014-2015 H5Nx high pathogenicity avian influenza (HPAI) outbreak affected 211 commercial premises, 21 backyard flocks, 75 individual wild birds and four captive-reared raptors in 21 Western and upper Midwestern states, resulting in death or culling of over 50.4 million poultry in the stamping-out programme that cost the US government $850 million. The outbreak had a negative $3.3 billion impact on the economy. Seventeen trading partners suspended imports of all US-origin poultry and poultry products while 38 trading partners regionalized the United States, and allowed trade in poultry and poultry products to continue from areas of the US not affected by HPAI. Disease response and control activities in addition to the use of comprehensive surveillance and regionalization (zoning) as prescribed by the OIE Terrestrial Animal Health Code are a scientifically valid and effective means to maintain safe trade in poultry and poultry products. This was further realized during the 2016 H7N8 HPAI outbreak in Dubois County, Indiana, with greater acceptance of regionalization and continuity in trade with a more limited cost of $30 million for eradication.

The Perceived Value of Passive Animal Health Surveillance: The Case of Highly Pathogenic Avian Influenza in Vietnam.

Economic evaluations are critical for the assessment of the efficiency and sustainability of animal health surveillance systems and the improvement of their efficiency. Methods identifying and quantifying costs and benefits incurred by public and private actors of passive surveillance systems (i.e. actors of veterinary authorities and private actors who may report clinical signs) are needed. This study presents the evaluation of perceived costs and benefits of highly pathogenic avian influenza (HPAI) passive surveillance in Vietnam. Surveys based on participatory epidemiology methods were conducted in three provinces in Vietnam to collect data on costs and benefits resulting from the reporting of HPAI suspicions to veterinary authorities. A quantitative tool based on stated preference methods and participatory techniques was developed and applied to assess the non-monetary costs and benefits. The study showed that poultry farmers are facing several options regarding the management of HPAI suspicions, besides reporting the following: treatment, sale or destruction of animals. The option of reporting was associated with uncertain outcome and transaction costs. Besides, actors anticipated the release of health information to cause a drop of markets prices. This cost was relevant at all levels, including farmers, veterinary authorities and private actors of the upstream sector (feed, chicks and medicine supply). One benefit associated with passive surveillance was the intervention of public services to clean farms and the environment to limit the disease spread. Private actors of the poultry sector valued information on HPAI suspicions (perceived as a non-monetary benefit) which was mainly obtained from other private actors and media.

Cost-benefit analysis of avian influenza control in Nepal.

Numerous outbreaks of highly pathogenic avian influenza A strain H5N1 have occurred in Nepal since 2009 despite implementation of a national programme to control the disease through surveillance and culling of infected poultry flocks. The objective of the study was to use cost-benefit analysis to compare the current control programme (CCP) with the possible alternatives of: i) no intervention (i.e., absence of control measures [ACM]) and ii) vaccinating 60% of the national poultry flock twice a year. In terms of the benefit-cost ratio, findings indicate a return of US $1.94 for every dollar spent in the CCP compared with ACM. The net present value of the CCP versus ACM, i.e., the amount of money saved by implementing the CCP rather than ACM, is US $861,507 (the benefits of CCP [prevented losses which would have occurred under ACM] minus the cost of CCP). The vaccination programme yields a return of US $2.32 for every dollar spent when compared with the CCR The net present value of vaccination versus the CCP is approximately US $12 million. Sensitivity analysis indicated thatthe findings were robust to different rates of discounting, whereas results were sensitive to the assumed market loss and the number of birds affected in the outbreaks under the ACM and vaccination options. Overall, the findings of the study indicate that the CCP is economically superior to ACM, but that vaccination could give greater economic returns and may be a better control strategy. Future research should be directed towards evaluating the financial feasibility and social acceptability of the CCP and of vaccination, with an emphasis on evaluating market reaction to the presence of H5N1 infection in the country.

Calculating the burden of disease of avian-origin H7N9 infections in China.

OBJECTIVE: A total of 131 cases of avian-originated H7N9 infection have been confirmed in China mainland from February 2013 to May 2013. We calculated the overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of comprehensive burden of disease in the 21st century from an acute animal-borne emerging infectious disease. DESIGN: We present an accurate and operable method for estimating the burden of H7N9 cases in China. The main drivers of economic loss were identified. Costs were broken down into direct (outpatient and inpatient examination and treatment) and indirect costs (cost of disability-adjusted life years (DALYs) and losses in the poultry industry), which were estimated based on field surveys and China statistical year book. SETTING: Models were applied to estimate the overall burden of H7N9 cases in China. PARTICIPANTS: 131 laboratory-confirmed H7N9 cases by 31 May 2013. OUTCOME MEASURE: Burden of H7N9 cases including direct and indirect losses. RESULTS: The total direct medical cost was ¥16 422 535 (US$2 627 606). The mean cost for each patient was ¥10 117 (US$1619) for mild patients, ¥139 323 (US$22 292) for severe cases without death and ¥205 976 (US$32 956) for severe cases with death. The total cost of DALYs was ¥17 356 561 (US$2 777 050). The poultry industry losses amounted to ¥7.75 billion (US$1.24 billion) in 10 affected provinces and ¥3.68 billion (USD$0.59 billion) in eight non-affected adjacent provinces. CONCLUSIONS: The huge poultry industry losses followed live poultry markets closing down and poultry slaughtering in some areas. Though the proportion of direct medical losses and DALYs losses in the estimate of H7N9 burden was small, the medical costs per case were extremely high (particularly for addressing the use of modern medical devices). A cost-effectiveness assessment for the intervention should be conducted in a future study.

Economic analysis of HPAI control in the Netherlands II: comparison of control strategies.

A combined epidemiological-economic modelling approach was used to analyse strategies for highly pathogenic avian influenza (HPAI) control for the Netherlands. The modelling framework used was InterSpread Plus (ISP), a spatially based, stochastic and dynamic simulation model. A total of eight control strategies were analysed, including pre-emptive depopulation and vaccination strategies. The analysis was carried out for three different regions in the Netherlands: high-, medium- and low-density areas (HDA, MDA and LDA, respectively). The analysis included the veterinary impact (e.g. number of infected premises and duration), but was particularly focused on the impact on direct costs (DC) and direct consequential costs. The efficient set of control strategies for HDA and MDA included strategies based on either pre-emptive depopulation only or combined vaccination and pre-emptive depopulation: D2 (pre-emptive depopulation within a radius of 2 km), RV3 + D1 (ring vaccination within a radius of 3 km and additional pre-emptive depopulation within a radius of 1 km) and PV + D1 (preventive vaccination in non-affected HDAs and pre-emptive depopulation within a radius of 1 km in the affected HDA). Although control solely based on depopulation in most cases showed to be effective for LDA, pre-emptive depopulation showed to have an additional advantage in these areas, that is, prevention of 'virus jumps' to other areas. The pros and cons of the efficient control strategies were discussed, for example, public perception and risk of export restrictions. It was concluded that for the Netherlands control of HPAI preferably should be carried out using strategies including pre-emptive depopulation with or without vaccination. Particularly, the short- and long-term implications on export, that is, indirect consequential costs (ICC) and aftermath costs of these strategies, should be analysed further.

The scientific rationale for the World Organisation for Animal Health standards and recommendations on avian influenza.

The World Organisation for Animal Health (OIE) prescribes standards for the diagnosis and control of avian influenza, as well as health measures for safe trade in birds and avian products, which are based on up-to-date scientific information and risk management principles, consistent with the role of the OIE as a reference standard-setting body for the World Trade Organization (WTO). These standards and recommendations continue to evolve, reflecting advances in technology and scientific understanding of this important zoonotic disease. The avian influenza viruses form part of the natural ecosystem by virtue of their ubiquitous presence in wild aquatic birds, a fact that human intervention cannot change. For the purposes of the Terrestrial Animal Health Code (Terrestrial Code), avian influenza is defined as an infection of poultry. However, the scope of the OIE standards and recommendations is not restricted to poultry, covering the diagnosis, early detection and management of avian influenza, including sanitary measures for trade in birds and avian products. The best way to manage avian influenza-associated risks to human and animal health is for countries to conduct surveillance using recommended methods, to report results in a consistent and transparent manner, and to applythe sanitary measures described in the Terrestrial Code. Surveillance for and timely reporting of avian influenza in accordance with OIE standards enable the distribution of relevant, up-to-date information to the global community.

Economic epidemiology of avian influenza on smallholder poultry farms.

Highly pathogenic avian influenza (HPAI) is often controlled through culling of poultry. Compensating farmers for culled chickens or ducks facilitates effective culling and control of HPAI. However, ensuing price shifts can create incentives that alter the disease dynamics of HPAI. Farmers control certain aspects of the dynamics by setting a farm size, implementing infection control measures, and determining the age at which poultry are sent to market. Their decisions can be influenced by the market price of poultry which can, in turn, be set by policy makers during an HPAI outbreak. Here, we integrate these economic considerations into an epidemiological model in which epidemiological parameters are determined by an outside agent (the farmer) to maximize profit from poultry sales. Our model exhibits a diversity of behaviors which are sensitive to (i) the ability to identify infected poultry, (ii) the average price of infected poultry, (iii) the basic reproductive number of avian influenza, (iv) the effect of culling on the market price of poultry, (v) the effect of market price on farm size, and (vi) the effect of poultry density on disease transmission. We find that under certain market and epidemiological conditions, culling can increase farm size and the total number of HPAI infections. Our model helps to inform the optimization of public health outcomes that best weigh the balance between public health risk and beneficial economic outcomes for farmers.

Optimal isolation control strategies and cost-effectiveness analysis of a two-strain avian influenza model.

The most important and effective measures against disease outbreaks in the absence of valid medicines or vaccine are quarantine and isolation strategies. In this paper optimal control theory is applied to a system of ordinary differential equation describing a two-strain avian influenza transmission via the Pontryagin's Maximum Principle. To this end, a pair of control variables representing the isolation strategies for individuals with avian and mutant strains were incorporated into the transmission model. The infection averted ratio (IAR) and the incremental cost-effectiveness ratio (ICER) were calculated to investigate the cost-effectiveness of all possible combinations of the control strategies. The simulation results show that the implementation of the combination strategy during the epidemic is the most cost-effective strategy for avian influenza transmission. This is followed by the control strategy involving isolation of individuals with the mutant strain. Also observed was the fact that low mutating and more virulent virus results in an increased control effort of isolating individuals with the avian strain; and high mutating with more virulent virus results in increased efforts in isolating individuals with the mutant strain.