Risk signals of an influenza pandemic caused by highly pathogenic avian influenza subtype H5N1: spatio-temporal perspectives

Highly pathogenic avian influenza (HPAI) subtype H5N1 is a trans-boundary animal disease that has crossed the animal-human species barrier and over the past decade has had a considerable impact on the poultry industry, wild bird populations and on human health. Understanding the spatio-temporal patterns of H5N1 outbreaks can provide visual clues to the dynamics of disease spread and of areas at risk, and thus improve the cost-effectiveness of disease control and prevention. This study describes the characteristics and investigates the temporal, spatial and space-time dynamics of H5N1 outbreaks in domestic poultry between December 2003 and December 2009 using a global database. The study found that the start date of the epidemic wave was postponed, the duration of the epidemic was prolonged and its magnitude reduced over time, but the disease transmission cycle was not efficiently interrupted. Two 'hot-spot' regions of H5N1 outbreaks were identified: well-documented locations in East and Southeast Asia, as well as a novel location at the boundaries of Europe and Africa, where enhanced surveillance should be conducted. The risk of a pandemic due to H5N1 remains high.     

The spread of highly pathogenic avian influenza (subtype H5N1) clades in Bangladesh, 2010 and 2011

Since the global spread of highly pathogenic avian influenza H5N1 during 2005–2006, control programs have been successfully implemented in most affected countries. HPAI H5N1 was first reported in Bangladesh in 2007, and since then 546 outbreaks have been reported to the OIE. The disease has apparently become endemic in Bangladesh. Spatio-temporal information on 177 outbreaks of HPAI H5N1 occurring between February 2010 and April 2011 in Bangladesh, and 37 of these outbreaks in which isolated H5N1 viruses were phylogenetically characterized to clade, were analyzed.     

Legislation for the control of avian influenza in the European union

In the light of experience gained with avian influenza (AI) outbreaks in Europe and elsewhere in the world, the European Union (EU) legislation has recently been updated. The strategy to control the introduction and spread of AI relies on rapid disease detection, killing of infected birds, movement restrictions for live birds and their products, cleaning and disinfection and vaccination. Measures are not only to be implemented in case of outbreaks of highly pathogenic AI (HPAI), but are now also directed against occurrence of low pathogenic AI of H5 and H7 (LPAI) subtypes in poultry, albeit in a modified manner proportionate to the risk posed by these pathotypes. Enhanced surveillance in poultry holdings and wild birds, as well as preventive vaccination, has also been introduced. EU Measures are flexible and largely based on risk assessment of the local epidemiological situation. The occurrence of HPAI H5N1 of the Asian lineage in the EU and its unprecedented spread by wild migratory birds necessitated the adoption of additional control measures. Although HPAI H5N1 has affected wild birds and poultry holdings in several EU Member States, EU legislation and its implementation in Member States has so far successfully limited the impact of the disease on animal and human health.     

Risk-based surveillance for H5N1 avian influenza virus in wild birds in Great Britain

Recent outbreaks of the H5N1 strain of avian influenza in Europe have highlighted the need for continuous surveillance and early detection to reduce the likelihood of a major outbreak in the commercial poultry industry. In Great Britain (gb), one possible route by which H5N1 could be introduced into domestic poultry is through migratory wild birds from Europe and Asia. Extensive monitoring data on the 24 wild bird species considered most likely to introduce the virus into GB, and analyses of local poultry populations, were used to develop a risk profile to identify the areas where H5N1 is most likely to enter and spread to commercial poultry. The results indicate that surveillance would be best focused on areas of Norfolk, Suffolk, Lancashire, Lincolnshire, south-west England and the Welsh borders, with areas of lower priority in Anglesey, south-west Wales, north-east Aberdeenshire and the Firth of Forth area of Scotland. These areas have significant poultry populations including a large number of free-range flocks, and a high abundance of the 24 wild bird species.     

Molecular epidemiology of avian influenza viruses circulating among healthy poultry flocks in farms in northern Vietnam

Repeated epizootics of highly pathogenic avian influenza (HPAI) virus subtype H5N1 were reported from 2003 to 2005 among poultry in Vietnam. More than 200 million birds were killed to control the spread of the disease. Human cases of H5N1 infection have been sporadically reported in an area where repeated H5N1 outbreaks among birds had occurred. Subtype H5N1 strains are established as endemic among poultry in Vietnam, however, insights into how avian influenza viruses including the H5N1 subtype are maintained in endemic areas is not clear. In order to determine the prevalence of different avian influenza viruses (AIVs), including H5N1 circulating among poultry in northern Vietnam, surveillance was conducted during the years 2006-2009. A subtype H5N1 strain was isolated from an apparently healthy duck reared on a farm in northern Vietnam in 2008 and was identified as an HPAI. Although only one H5N1 virus was isolated, it supports the view that healthy domestic ducks play a pivotal role in maintaining and transmitting H5N1 viruses which cause disease outbreaks in northern Vietnam. In addition, a total of 26 AIVs with low pathogenicity were isolated from poultry and phylogenetic analysis of all the eight gene segments revealed their diverse genetical backgrounds, implying that reassortments have occurred frequently among strains in northern Vietnam. It is, therefore, important to monitor the prevalence of influenza viruses among healthy poultry between epidemics in an area where AIVs are endemic.     

Geostatistical visualisation and spatial statistics for evaluation of the dispersion of epidemic highly pathogenic avian influenza subtype H5N1

The aim of this study was to evaluate a range of statistical and geostatistical methods for their usefulness in providing insights into how highly pathogenic avian influenza (HPAI) subtype H5N1 might spread through a national population of village poultry. The insights gained allow the generation of disease dispersion hypotheses. The case study data set consisted of 161 outbreaks of HPAI subtype H5N1 in village poultry reported in Romania between October 2005 and June 2006. Reports of village outbreaks (%) occurred in three waves: October-December (14%), February-March (16%), and May-June (68%). Risk mapping - based on variography and kriging - was used to visualize the evolution of the epidemic. Outbreaks first appeared in eastern and southern Romania, particularly within an area that forms part of the Danube River Delta. The largest phase of the epidemic affected villages in all parts of central, southern, and eastern Romania, but outbreaks were clustered in central Romania. Outbreaks spread in an east to west direction. By using geostatistical visualisation and spatial statistics, the evolution of the epidemic could be characterised into two parts: disease introduction, local spread, and sporadic outbreaks, and long-distance disease spread with rapid epidemic propagation. This is consistent with the hypothesis that the environment and landscape (specifically the Danube River Delta) played a critical role in the introduction and initial spread of HPAI subtype H5N1 during the autumn and winter of 2005, and that the movement of poultry might have introduced the infection into central Romania during the spring and summer of 2006. Further research focusing on the spatio-temporal interface between the two parts of the epidemic might reveal how and why it progressed from a confined, local epidemic to a large, national epidemic. Such information would assist efforts to limit the global spread of HPAI subtype H5N1.     

H5N1亚型禽流感病毒对鸭的致病性研究

为评估H5N1亚型禽流感病毒(AIV)在实验室环境下对鸭的致病力,本研究以无特殊病原(SPF)鸭为模型,对我国近年分离的7株病毒进行了致病力分析。结果发现其中4株病毒对鸭致死率为100%,2株病毒对鸭的致死率分别为60%和80%,另外1株病毒,A/goose/Hubei/51/05(GS/HB/51/05),对鸭无致病力。本研究还发现,与高致病力毒株一样,GS/HB/51/05也可在鸭体内呈全身性复制,并且可通过喉头和泻殖腔向外排泄。我们推测GS/HB/51/05可能是中国南方出现的其他对鸭呈高致病力的H5N1病毒的祖先,对这些病毒的系统研究,可揭示H5N1亚型AIV对鸭的致病力遗传机制。     

Swine influenza viruses isolated in 1983, 2002 and 2009 in Sweden exemplify different lineages

Swine influenza virus isolates originating from outbreaks in Sweden from 1983, 2002 and 2009 were subjected to nucleotide sequencing and phylogenetic analysis. The aim of the studies was to obtain an overview on their potential relatedness as well as to provide data for broader scale studies on swine influenza epidemiology. Nonetheless, analyzing archive isolates is justified by the efforts directed to the comprehension of the appearance of pandemic H1N1 influenza virus. Interestingly, this study illustrates the evolution of swine influenza viruses in Europe, because the earliest isolate belonged to ''classical'' swine H1N1, the subsequent ones to Eurasian ''avian-like'' swine H1N1 and reassortant ''avian-like'' swine H1N2 lineages, respectively. The latter two showed close genetic relatedness regarding their PB2, HA, NP, and NS genes, suggesting common ancestry. The study substantiates the importance of molecular surveillance for swine influenza viruses.     

Epidemiological findings of outbreaks of disease caused by highly pathogenic H5N1 avian influenza virus in poultry in Egypt during 2006

This paper describes the first threats of H5N1 avian influenza outbreaks in Egypt recorded from February to December 2006 in commercial and domestic poultry from different species and summarizes the major characteristics of the outbreak. There were 1024 cases from different poultry species (rural and commercial chickens of different breeding types, turkeys, ducks, geese, and quail) either in commercial breeding or in backyards from different locations in Egypt. All tested positive for the H5N1 subtype. From these cases only 12 avian influenza A viruses were isolated and characterized from samples collected during outbreaks. All isolates were characterized, and the data confirmed that the isolated viruses belong to highly pathogenic avian influenza of subtype H5N1. Full hemagglutinin (HA) gene (segment 4) sequencing was also done, and the sequences of these isolates were compared with other strains from Russia, Africa, and the Middle East. The data revealed that all Egyptian strains were very closely related and belonging to subclade 2.2 of the H5N1 virus of Eurasian origin, the same one circulating in the Middle East region and introduced into Africa at the beginning of 2006. This study showed evidence of the wide spread of H5N1 virus infection in domestic poultry in Egypt within a short time. The most obvious features of these outbreaks were severe clinical signs and high mortalities as well as very rapid and widespread occurrence within the country in a very short time. The possible causes of its rapid spread and prospects of disease control are discussed.     

Epidemiology of H5N1 avian influenza

High pathogenic (HP) H5N1 avian influenza (AI) infection has been reported in domestic poultry, wildlife, and human populations since 1996. Risk of infection is associated with direct contact with infected birds. The mode of H5N1 spread from Asia to Europe, Africa and the Far East is unclear; risk factors such as legal and illegal domestic poultry and exotic bird trade, and migratory bird movements have been documented. Measures used to control disease such as culling, stamping out, cleaning and disinfection, and vaccination have not been successful in eradicating H5N1 in Asia, but have been effective in Europe.     

Isolation of Haemophilus somnus from dairy cattle in kwaZulu-Natal. An emerging cause of 'dirty cow syndrome' and infertility?

Haemophilus somnus was consistently isolated from vaginal discharges of dairy cows submitted from field cases of vaginitis, cervicitis and/or metritis in the KwaZulu-Natal Midlands during the period July 1995 - December 2000 and from the East Griqualand area in November/December 2000. The purulent vaginal discharges, red granular vaginitis and cervicitis, and pain on palpation described in these cases was very similar to that reported in outbreaks of H.somnus endometritis syndrome in Australia, Europe and North America. In all the herds involved in these outbreaks, natural breeding with bulls was employed. Although there was a good cure rate in clinically-affected animals treated with tetracyclines, culling rates for chronic infertility were unacceptably high. Employment of artificial insemination in these herds improved pregnancy rates in cows that had calved previously, but many cows that had formerly been infected failed to conceive.     

Emergence of H3N2 reassortant influenza A viruses in North American pigs

In late summer through early winter of 1998, there were several outbreaks of respiratory disease in the swine herds of North Carolina, Texas, Minnesota and Iowa. Four viral isolates from outbreaks in different states were analyzed, both antigenically and genetically. All of the isolates were identified as H3N2 influenza viruses with antigenic profiles similar to those of recent human H3 strains. Genotyping and phylogenetic analysis demonstrated that the four swine viruses had emerged through two different pathways. The North Carolina isolate is the product of genetic reassortment between human and swine influenza viruses, while the others arose from reassortment of human, swine and avian viral genes. The hemagglutinin genes of the four isolates were all derived from the human H3N2 virus circulating in 1995. It remains to be determined if either of these recently emerged viruses will become established in the pigs in North America and whether they will become an economic burden.     

Highly pathogenic avian influenza H5N1 virus in cats and other carnivores

The Asian lineage highly pathogenic avian influenza (HPAI) H5N1 virus is a known pathogen of birds. Only recently, the virus has been reported to cause sporadic fatal disease in carnivores, and its zoonotic potential has been dominating the popular media. Attention to felids was drawn by two outbreaks with high mortality in tigers, leopards and other exotic felids in Thailand. Subsequently, domestic cats were found naturally infected and experimentally susceptible to H5N1 virus. A high susceptibility of the dog to H3N8 equine influenza A virus had been reported earlier, and recently also HPAI H5N1 virus has been identified as a canine pathogen. The ferret, hamster and mouse are suitable as experimental animals; importantly, these species are also kept as pets. Experimental intratracheal and oral infection of cats with an HPAI H5N1 virus isolate from a human case resulted in lethal disease; furthermore, cats have been infected by the feeding of infected chickens. Spread of the infection from experimentally infected to in-contact cats has been reported. The epidemiological role of the cat and other pet animal species in transmitting HPAI H5N1 virus to humans needs continuous consideration and attention.     

我国H5和H7N9亚型高致病性禽流感的监测及疫情暴发分析

禽流感病毒（avian influenza virus,AIV）是一种重要的人兽共患病病原,严重制约养禽业的健康发展,并对公共卫生安全构成极大威胁。其中,H5（H5N1、H5N2、H5N6、H5N8等）和H7N9亚型高致病性禽流感病毒（highly pathogenic avian influenza virus,HPAIV）引起的高致病性禽流感（highly pathogenic avian influenza,HPAI）对我国养禽业危害巨大。通过实施强制免疫,疫情得到了控制,但在禽群中仍散状暴发,并出现多种新型病毒,防控形势依然严峻。本文总结了截至2021年9月我国禽类暴发H5和H7N9亚型HPAI的所有官方公布的疫情暴发事件以及监测数据,分析了其流行特点,以期为禽流感的预警和防控提供参考。     

Newcastle disease and avian influenza A virus in wild waterfowl in South Africa

In an intensive ostrich farming area in South Africa with a history of ostrich influenza outbreaks, we conducted a survey of avian influenza virus (AIV) and Newcastle disease virus (NDV) in wild aquatic birds. During late autumn and winter 1998, the time of year when outbreaks in ostriches typically start to occur, 262 aquatic birds comprising 14 species were sampled and tested for both virus infections. From eight samples, AIV, serotype H10N9, could be isolated. All isolates were apathogenic as determined by the intravenous pathogenicity index (0.00). Conversely, none of 33 sera of these wild birds showed antibodies against H10. However, one bird was found serologically positive for H6 AIV. This AIV serotype was later isolated from ostriches during an avian influenza outbreak in this area. No NDV was isolated although 34 of 46 serum samples contained NDV-specific antibodies. This is the first H10N9 isolate to be reported from Africa. In addition, our data support the notion that wild aquatic birds may function as a reservoir for AIV and NDV in South Africa.     

Vaccine failure caused an outbreak of equine influenza in Croatia

In April 2004 an outbreak of equine influenza occurred at the Zagreb hippodrome, Croatia. Clinical respiratory disease of the same intensity was recorded in vaccinated and non-vaccinated horses. The equine influenza vaccine used in Croatia at the time of the outbreak contained the strains A/equine/Miami/63 (H3N8), A/equine/Fontainebleau/79 (H3N8) and A/equine/Prague/56 (H7N7). At the same time, the usual strains in vaccines used in Europe were, in accordance with the recommendation of the World Organisation for Animal Health (OIE) Expert Surveillance Panel on equine influenza, A/equine/Newmarket/1/93 (H3N8) and A/equine/Newmarket/2/93 (H3N8). At the same time, some current vaccines in the USA contained A/equine/Kentucky/97 (H3N8). Genetic characterization of the HA1 portion of the haemagglutinin (HA) gene of virus isolated from the outbreak indicated that the isolate (A/equine/Zagreb/04) was an H3N8 strain closely related to recent representative viruses of the American lineage Florida sub-lineage. In comparison with both H3N8 vaccine strains used in horses at the Zagreb hippodrome, A/equine/Zagreb/04 displayed amino acids changes localised to 4 of the 5 described antigenic sites (A-D) of subunit protein HA1. Comparison of the amino acid sequence of the HA1 subunit protein of the outbreak strain with that of A/equine/Newmarket/1/93 displayed three amino acids changes localised in antigenic sites B and C, while antigenic sites A, D and E were unchanged. The Zagreb 2004 outbreak strain had the same amino acids at antigenic sites of the HA1 subunit protein as the strain A/equine/Kentucky/97. Amino acid changes in antigenic sites between HA1 subunit of the outbreak strain and the strains used in the vaccines likely accounted for the vaccine failure and the same clinical signs in vaccinated and unvaccinated horses. Use of a recent strain in vaccines should limit future outbreaks.     

Retrospective analysis of serum and nasal mucus from cattle in Northern Ireland for evidence of infection with influenza A virus

Eighty-four pairs of acute and convalescent serum samples collected in 1998 and 1999 from 17 outbreaks of respiratory disease, milk drop syndrome or diarrhoea in cattle were tested by haemagglutination inhibition against human influenza viruses A/Eng/333/80 (HIN1) and A/Eng/427/88 (H3N2). Antibodies to these viruses were present in the convalescent sera of 56.5 per cent and 58.8 per cent cattle tested, respectively, with 56 per cent of the animals seroconverting to one or both viruses. Titres were typically higher to A/Eng/427/88 (H3N2). Further testing of a subset of 21 of these serum pairs against the predominant H1N1 and H3N2 human and porcine strains circulating when the samples were collected revealed that the highest reactivity, in terms of both the magnitude of the recorded titres and the number of positive sera, was to human H3N2 strains. The titres to human H1N1 strains and to both porcine subtypes were low or absent. Attempts to isolate influenza A virus from nasal mucus or swab samples from 142 cattle from 46 cases of respiratory disease and/or milk drop syndrome by passage in embryonated specific pathogen-free eggs were unsuccessful.     

Estimating the risk of importation of foot-and-mouth disease into Europe

The opinions of a number of recognised world experts on foot-and-mouth disease (FMD) were sought in order to answer key questions relating to the importation of the disease into European countries from countries outside Europe. In addition, their opinions were sought on where in Europe a primary outbreak of FMD was most likely to occur and the number of outbreaks likely to occur within European countries in the next five years. The Balkans group of countries was considered to be the most likely group within Europe to have a primary outbreak of FMD and also most likely to have the highest number of primary outbreaks. Turkey was considered to be the country outside Europe which was most likely to be the source of an outbreak within Europe as a whole, and the illegal importation of livestock was considered to be the most likely route of introduction of FMD into Europe. Results specific to the Islands group of countries, which included the UK and Ireland, suggested that this group was likely to have a mean of one primary outbreak of FMD in the five years from September 2000, and that the importation of foodstuffs by people entering those countries from Turkey was the most likely source of an outbreak.