One health: the Hong Kong experience with avian influenza.

The occurrence of avian influenza A(H5N1) in Hong Kong in 1997 led to the development of a "One-Health" approach to deal with emerging infectious diseases that has been applied to other emergent diseases such as SARS and the pandemic H1N1 2009. Evaluation of poultry marketing and production systems and investigations at the animal-human interface, led to defining the routes of human exposure to avian influenza and factors that allowed virus to multiply and persist. Active and systematic surveillance of apparently healthy as well as diseased poultry and wild birds provided evidence of ongoing virus evolution in the wider region. Epidemiological studies, supplemented with molecular epidemiology, helped to elucidate the role of the poultry marketing system and live poultry markets in the persistence of avian influenza viruses and provided evidence for the impact of interventions designed to interrupt virus transmission. Enhanced bio-security, active surveillance together with targeted and evidence-based interventions in the poultry production, and marketing system together with poultry vaccination has prevented further human H5N1 disease and minimized outbreaks of poultry disease in Hong Kong. Similar strategies have led to the understanding of the emergence of SARS and provided options for preventing the re-emergence of this disease. Surveillance of influenza in swine has provided insights into the emergence of the 2009 pandemic, to the reverse zoonosis of the pandemic virus from humans to swine and to the emergence of novel reassortant viruses within swine. "One Health" strategies are not "cost-free" and require sensitive implementation to optimize food-safety and food security, while safeguarding the economics of animal husbandry and the environment and remaining sensitive to cultural practices.

H5N1 highly pathogenic avian influenza in Indonesia: retrospective considerations.

Indonesia is one of the five countries where highly pathogenic avian influenza viruses of the H5N1 subtype (H5N1 HPAI) remain endemic in poultry. Importantly, it is one of the countries where the virus causes human infections. WHO data indicate that as of 2 May 2012, 189 human cases of Influenza A (H5N1) had been reported in Indonesia, with 157 human deaths. These human cases included a small number in which limited human-to-human transmission could have occurred. Hence, there remains a critical need in Indonesia for a more effective One Health approach to the control and prevention of this disease in people and in poultry. This chapter explores a number of aspects of the evolution of this disease in Indonesia, the virus that causes it and the control and preventive measures introduced, focusing on the successes and shortcomings of veterinary and One Health approaches. Indonesia provides many examples of situations where this latter approach has been successful, and others where further work is needed to maximize the benefits from coordinated responses to this disease leading to effective management of the risk to human health.

Progress in control of H5N1 highly pathogenic avian influenza and the future for eradication.

Three broad factors, occurring concurrently, prevent elimination of highly pathogenic avian influenza caused by viruses of the H5N1 subtype (H5N1 HPAI) in countries and subregions where infection has remained endemic. These factors are the nature of the poultry sector, the quality of veterinary and animal production services (both public and private) serving the poultry industry, and the extent and level of commitment at all levels to virus elimination. Most of these countries have developed and adopted programs for progressive control of H5N1 HPAI, focused on the local factors hindering elimination of the viruses. Based on the rate of implementation of these measures over the last 5 to 7 yr (during which time there has been unprecedented financial and technical support from the international donor community), it is not expected that global eradication of H5N1 HPAI viruses can be achieved within the next 10 yr. If the "classical" approach to control, based around early case detection and culling, were adopted in a zone containing millions of free-running ducks, the work load required to complete even the first round of testing would exceed existing capacity. There would be no guarantees of sustained success locally, especially if the viruses are not eradicated regionally.

Experiences with vaccination in countries endemically infected with highly pathogenic avian influenza: the Food and Agriculture Organization perspective.

Vaccination has been used extensively for the control and prevention of highly pathogenic avian influenza (HPAI) caused by viruses of the H5N1 subtype in endemically infected countries. The Food and Agriculture Organization views vaccination as a legitimate aid in the control and prevention of infection and disease caused by HPAI viruses but does not see it as a panacea. Vaccination should be used as just one in a number of measures used together to reduce the effect and risk of infection. It will be required for a considerable time in endemically infected countries. The methods used in Vietnam in implementing blanket vaccination against H5N1 HPAI viruses demonstrate the steps that should be considered when introducing vaccination. So far, it has not been possible to determine the precise effect of vaccination in endemically infected countries because it has been used in combination with other measures. Well managed vaccination campaigns will reduce the incidence of infection in poultry and therefore reduce the risk to humans from these viruses. Vaccination was implemented to protect both poultry and humans, with a major goal being to reduce the risk of emergence of a human influenza pandemic virus. Economic analysis of vaccination should focus on cost-effectiveness of proposed strategies. Ex-ante and ex-post evaluation of vaccination campaigns should take into account the benefits generated in the poultry sector and for human health.

Lessons learned from Asian H5N1 outbreak control.

Numerous lessons have been learned so far in controlling H5N1 avian influenza in Asia. Early detection of incursions of virus prevented establishment of the disease in several countries, notably Japan, South Korea, and Malaysia. In countries where detection of early cases was delayed, infection is endemic and has been for three or more years. Control measures implemented in these countries need to reflect this finding. Vaccination will continue to be one of the key measures used in these endemically infected countries. Used alone, vaccination will not result in elimination of H5N1 viruses from a country, but, if used correctly, it will markedly reduce the prevalence of and susceptibility to infection. Vaccination has already played a valuable role in reducing the adverse effects of H5N1 viruses. Mass culling also reduces the level of infection in infected areas. However, the long-term benefits are limited in endemically infected countries owing to the high probability of reinfection on restocking unless other measures are used in parallel. Full epidemiological studies have not been conducted in many infected countries. Nevertheless, it is recognized that the number of clinical cases does not truly reflect the levels of infection. Domestic ducks and large live poultry markets have played a key role in the persistence of infection, because they can be infected silently. In tackling this disease, countries should adopt integrated control programs using the combination of measures best suited to the local environment. All surveillance data should be shared, both positive and negative, and should include information on cases of infection and disease. Socioeconomic and ecological implications of all control measures should be assessed before implementation, especially the impact on the rural poor.

Experience in control of avian influenza in Asia.

Highly pathogenic H5N1 avian influenza viruses have been circulating in Asia for over ten years, providing considerable experience on which to base appropriate long-term strategies for their control. Experience in Hong Kong SAR demonstrates that existing production and marketing practices should be changed and a range of parallel measures used. It also shows the extent of surveillance required to ensure continuing freedom from infection. Certain high-risk practices should be changed or otherwise overcome in order to control and prevent disease, including intensive rearing of large numbers of poultry in premises without biosecurity commensurate with the level of risk for exposure; complex market chains involving many smallholders selling poultry through large numbers of transporters and middlemen in poorly regulated live poultry markets; and rearing of large numbers of ducks outdoors. These high-risk practices are compounded by weak veterinary services and poor reporting systems. In many parts of Asia, these methods of rearing and marketing are an integral way of life, support the poorest members of the community or cannot be changed quickly without severe socioeconomic consequences. The gains made so far will be ephemeral unless there is a shift from an emergency focus to one of consolidation in which these high-risk practices are identified and sustainable measures implemented to minimize the risks they pose, taking account of the socioeconomic effects of interventions. Vaccination will play a key role, as it currently does in China and Viet Nam.

Disease intelligence for highly pathogenic avian influenza.

A comprehensive approach to highly pathogenic avian influenza (HPAI) is crucial for identifying all the factors that contribute to its emergence, spread and persistence. Epidemiological understanding makes it possible to predict the evolution of the virus and to prevent and control the socioeconomic, environmental, institutional and policy consequences. At FAO, risk assessment and intelligence with regard to HPAI are based on lessons learnt from assisting countries to design strategies and on implementation of technical assistance programmes, which reveal important elements, such as the roles of ducks, live-bird markets and trade. Wild birds were found to contribute, by transporting the H5N1 virus over long distances. The contributions of different poultry farming systems and market chains in the epidemiology of HPAI are well recognized; however, the respective roles of smallholder systems and commercial farms are unclear. FAO considers that smallholders will continue to be an important factor and should be taken into account in control and prevention programmes. Changes in poultry farming are essentially driven by the private sector and market forces and could have negative consequences on the livelihoods of smallholders and on ecologically balanced production systems and agricultural biodiversity. Biosecurity can, however, be improved at the level of farms and markets. Institutional factors, such as the capacity of animal health systems to deliver control programmes, are also important, requiring strengthening and innovation in risk analysis and management.

Use of avian influenza vaccination in Hong Kong.

Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.

Origin and evolution of highly pathogenic H5N1 avian influenza in Asia.

Outbreaks of highly pathogenic avian influenza caused by H5N1 viruses were reported almost simultaneously in eight neighbouring Asian countries between December 2003 and January 2004, with a ninth reporting in August 2004, suggesting that the viruses had spread recently and rapidly. However, they had been detected widely in the region in domestic waterfowl and terrestrial poultry for several years before this, and the absence of widespread disease in the region before 2003, apart from localised outbreaks in the Hong Kong Special Autonomous Region (SAR), is perplexing. Possible explanations include limited virus excretion by domestic waterfowl infected with H5N1, the confusion of avian influenza with other serious endemic diseases, the unsanctioned use of vaccines, and the under-reporting of disease as a result of limited surveillance. There is some evidence that the excretion of the viruses by domestic ducks had increased by early 2004, and there is circumstantial evidence that they can be transmitted by wild birds. The migratory birds from which viruses have been isolated were usually sick or dead, suggesting that they would have had limited potential for carrying the viruses over long distances unless subclinical infections were prevalent. However, there is strong circumstantial evidence that wild birds can become infected from domestic poultry and potentially can exchange viruses when they share the same environment. Nevertheless, there is little reason to believe that wild birds have played a more significant role in spreading disease than trade through live bird markets and movement of domestic waterfowl. Asian H5N1 viruses were first detected in domestic geese in southern China in 1996. By 2000, their host range had extended to domestic ducks, which played a key role in the genesis of the 2003/04 outbreaks. The epidemic was not due to the introduction and spread of a single virus but was caused by multiple viruses which were genotypically linked to the Goose/GD/96 lineage via the haemagglutinin gene. The H5N1 viruses isolated from China, including the Hong Kong SAR, between 1999 and 2004 had a range of genotypes and considerable variability within genotypes. The rising incidence and widespread reporting of disease in 2003/04 can probably be attributed to the increasing spread of the viruses from existing reservoirs of infection in domestic waterfowl and live bird markets leading to greater environmental contamination. When countries in the region started to report disease in December 2003, others were alerted to the risk and disease surveillance and reporting improved. The H5N1 viruses have reportedly been eliminated from three of the nine countries that reported disease in 2003/04, but they could be extremely difficult to eradicate from the remaining countries, owing to the existence of populations and, possibly, production and marketing sectors, in which apparently normal birds harbour the viruses.

Synthesis and anticonvulsant activity of enaminones. 3. Investigations on 4'-, 3'-, and 2'-substituted and polysubstituted anilino compounds, sodium channel binding studies, and toxicity evaluations.

In a continuing evaluation of the aniline-substituted enaminones, the synthesis of additional para-substituted analogs has been made in an attempt to further quantify the electronic (sigma) and lipophilic (pi) requirements for anticonvulsant activity in this series. In addition, meta- and ortho-substituted and polysubstituted compounds have been synthesized and evaluated for anticonvulsant activity. In the para-substituted series, 4-cyano analogs (32 and 33) (+ sigma, - pi), which were highly active via intraperitoneal (ip) injection in mice, were inactive on oral (po) administration in rats. The para-substituted trifluoromethoxy (+ sigma, + pi) analog (8) had significant potency by both routes. Meta substitution limited the activity due to steric factors. Bromo and iodo substituents produced active para-substituted analogs (5 and 17) but were inactive when substituted in the meta position (37 and 41, respectively). Ortho substitution provided no clear relationship due to nonparametric deviations. Neither 1, the prototype enaminone, nor 2, the putative metabolite, produced significant nephrotoxicity or hepatotoxicity. Sodium channel binding of 1 and 8 indicated that 8 displayed relatively potent sodium channel binding but 1 showed weaker effects with IC50 values of 489 and 170 microM respectively against [3H]batrachotoxinin A 20 alpha-benzoate ([3H]BTX-B).

Avian influenza in Hong Kong 1997-2002.

In 1997, a high-pathogenicity H5N1 avian influenza virus caused serious disease in both man and poultry in Hong Kong, China. Eighteen human cases of disease were recorded, six of which were fatal. This unique virus was eliminated through total depopulation of all poultry markets and chicken farms in December 1997. Other outbreaks of high-pathogenicity avian influenza (HPAI) caused by H5N1 viruses occurred in poultry in 2001 and 2002. These H5N1 viruses isolated had different internal gene constellations to those isolated in 1997. No new cases of infection or disease in man due to these or other H5N1 viruses have been reported. This paper provides an overview and chronology of the events in Hong Kong relating to avian influenza, covering the period from March 1997 to March 2002.

An update on avian influenza in Hong Kong 2002.

An outbreak of highly pathogenic avian influenza caused by multiple genotypes of H5N1 virus occurred in Hong Kong, commencing in January 2002. Infection in local chicken farms was preceded by the detection of virus in multiple retail markets and the main poultry wholesale market. The first case of this disease on a local farm was detected on February 1, 2002. By February 9, 2002, 15 farms were infected, and by late March a total of 22 infected farms had been identified. Three main clusters of infected farms were seen, suggesting multiple incursions of virus, and subsequent limited lateral spread to neighboring firms. Control of this disease has been effected through a combination of quarantine, tightening of biosecurity measures, and depopulation of infected and contact farms. About 950,000 birds have been destroyed. Vaccination using a killed H5 vaccine was introduced in April 2002 to farms in one zone where infection has persisted. None of the viruses isolated contained the internal genes found in the 1997 H5N1 virus.

Outbreak of botulism in horses.

An outbreak of nervous disease in Standardbred horses occurred near Bendigo, in south-eastern Australia, in October 1980. Over a two week period 11 horses in four training stables were affected with gait abnormalities, depression and recumbency. Eight of the 11 died. The results of an investigation implicated Clostridium botulinum toxin as the cause. The toxin was food-borne as a contaminant of oaten chaff.

Diseases of young captive crocodiles in Papua New Guinea.

To identify causes of mortality in young captive crocodiles, detailed necropsy and laboratory examination was done on 54 (30 Crocodylus porosus, 22 C. novaeguineae, 2 of unrecorded species). Although multiple infections often confounded interpretation it was concluded that the major infectious diseases, of approximately equal importance, were coccidiosis, bacterial septicaemia with Gram-negative organisms, and metazoan parasitism including ascariasis and pentastomiasis. A range of other lesions and agents was recognised, including keratitis, enteritis of unknown aetiology, non-suppurative encephalitis, traumatic peritonitis and trematodes located in renal tubules, gut and blood vessels. Some crocodiles in poor condition had only mild lesions associated with metazoan parasites and the cause of death or illness could not be clearly determined, although it was considered likely that adaptation failure was a contributing factor.

Trichinellosis in Papua New Guinea.

OBJECTIVES: To describe the discovery in a domestic pig of the first case of trichinellosis in Papua New Guinea, caused by a new taxon within the genus Trichinella (T papuae). Also, to establish if the disease occurred in the local wild pig population and in domestic pigs elsewhere in the country, and to test if the worm was infective to some other animals. PROCEDURE: Fresh and fixed tissue samples were examined by the digestion method and histologically, respectively, for the non-encapsulated larvae of T papuae. Feeding trials were conducted, using infected tissues and infective larvae, on animals under laboratory conditions. RESULTS: About 8.8% of a wild pig population in Western Province, adjacent to Irian Jaya, Indonesia, was found to be infected. Infection was not found in other local and feral animals or in domestic pigs from other parts of the country. Infection was experimentally established in cats, pigs and laboratory bred mice and rats. CONCLUSION: Trichinellosis is confined to one remote locality in PNG. Domestic pigs in the initial case became infected, probably, by eating infected wild pig meat.

Haemorrhagic necrotising enteritis in foals associated with Clostridium perfringens.

Two foals aged 35 and 48 h from 2 Thoroughbred studs died several hours after developing clinical signs of depression, severe haemorrhagic diarrhoea and dehydration. Both foals had an acute haemorrhagic enteritis extending from the anterior jejunum to the terminal ileum which was characterised histologically by villus necrosis. Necrotic villi were surrounded by large numbers of rod-shaped Gram positive bacteria. Clostridium perfringens was recovered from the intestines of both foals and the isolates were considered to be C. perfringens type C. Other cases of diarrhoea were also observed in foals of the same age on these 2 studs, but the aetiology of these was not determined.

Progressive interstitial pneumonia in goats.

Seven Anglo-Nubian goats, 5 months to 3 1/2 years old, developed clinical signs of increased respiratory rate, weight loss and exercise intolerance. Post-mortem examination of the goats revealed extensive consolidation of the lungs involving all lobes. Lesions, consisting of peribronchial and perivascular lymphoid cuffing, accumulations of homogeneous eosinophilic material in alveolar spaces, alveolar epithelialisation and thickening of alveolar septa as a result of lymphocytic infiltration, were detected histologically. A syncytial forming virus was consistently isolated from affected animals in explant cultures of lung, synovial membrane and choroid plexus. This agent had similar growth characteristics to the caprine arthritis-encephalitis (CAE) virus and the possible relationship between the respiratory disease and the diseases caused by the CAE virus is discussed.

Causes of preweaning mortality on a large intensive piggery.

Causes of preweaning mortality were examined on a large intensive piggery. Diagnosis was made using comprehensive clinical histories combined with post-mortem data. Two thousand four hundred and twenty-six piglets were born in 238 litters. Pre-parturient and parturient losses were 2.9% and 5.4% of the total numbers of piglets born. Birth to weaning mortality was 11.3%. Among piglets born alive, overlaying was the most frequent cause of death (2.1%), followed by deaths due to diarrhoea (1.7%), anaemia (1.2%), savaging (1.1%) and losses of small weak piglets (0.9%). Most deaths, including stillbirths, were associated with below average birth weight, and two-thirds of all deaths of liveborn pigs occurred within 4 days of birth. Increased litter size resulted in decreased birth weights, an increased percentage of stillborn piglets and mummified foetuses, but duration of parturition was not affected. Stillborn piglets were born late in the litter and after a longer interval between pigs born (interpig interval). Over 70% of deaths due to overlay were in previously healthy piglets, but some were associated with illness of the sow (18%) or both sow and piglet (3%). Savaging was confined mainly to first parity sows and was responsible for 20% of all deaths in these litters. Sixty-two per cent of all piglets with a birth weight of less than 800g were stillborn or died before weaning compared with 18.7% mortality for all piglets. Anaemia in piglets was considered to be due to umbilical haemorrhage. Anaemic piglets had a 36% mortality to weaning compared with 10% for non-anaemic piglets.(ABSTRACT TRUNCATED AT 250 WORDS)