For countries with endemic infection in poultry, it has been recommended that control and prevention (and eventual elimination) should be approached progressively using a measured and rational approach with a clearly defined strategy, objectives and an appropriate, adaptively managed, work plan. This recommendation was based on a review of the information on control measures available in 2008. Three country types were identified in which different approaches were required – those free from infection in poultry, those that are recently infected and those where virus is endemic. For those places free from virus in poultry, the focus is on appropriate preventive measures and development of systems for rapid case detection. For countries that are recently infected, the objective is rapid elimination of the virus from poultry, usually based around stamping out. Field evidence suggests that this approach has usually been successful given that most countries that reported disease caused by Influenza A (H5N1) viruses in the past 7 years have eliminated the virus. Only a small number of countries remain endemically infected but these are places with large, complex poultry production and marketing systems, and other constraints to virus elimination. Appropriate measures for these countries have been discussed in a report on countries where infection remains endemic. Three broad factors appear to be shared by these countries: the complex nature of the poultry production and marketing systems, limited veterinary capacity and low level of commitment (from producers to central government) to country-wide elimination of virus. These factors were believed to have favoured persistence of virus. The conclusions were based mainly on observations of the affected countries rather than purposive scientific studies. However, a number of the conclusions are supported by other studies aimed at identifying risk factors for infection across a number of countries or in individual countries.
The ‘classical’ approach to HPAI control and elimination based on early detection and stamping out has proved to be effective in most cases for elimination of HPAI and some low pathogenicity avian influenza (LPAI) viruses from poultry. It can result in large-scale destruction of poultry in affected areas with high concentrations of poultry as occurred in Canada, the Netherlands and Mexico in 2012. However, the persistence of H5N1 HPAI in Egypt, Indonesia, China, Vietnam and Bangladesh resulted in modifications to the approach to control and prevention of this disease because the viruses remained entrenched in these countries even after application of approaches based on stamping out.
Limited culling of known infected flocks and direct contacts has replaced wide-area culling in most countries with endemic infection in poultry, including Vietnam and China. Some other countries have also adopted this approach. Evidence for the benefits of limited culling includes successful programmes in Thailand (2004 onwards after the first wave of cases) and Hong Kong SAR (in outbreaks in 2001, 2002, 2003 and 2008 in which only a small number of farms were depopulated in contrast to the large-scale depopulation in 1997 involving all commercial farms).
A number of modelling studies on stamping out for avian influenza have been conducted and the results summarised. The value of any model depends on the quality of the data on which it is constructed and this has been a limiting factor for many of the models developed for avian influenza in Asia. Spatial models for outbreaks in the Netherlands, where good experimental and field data are available, suggest that only through mass culling can disease be eliminated in areas with very high poultry farm density and that focusing of stamping out on farms likely to generate high numbers of secondary cases is, potentially, a more effective strategy than other methods of culling. Models of transmission in Great Britain suggest that most outbreaks of HPAI would probably not proceed beyond the initial infected farm but, if a large outbreak occurred, wide-area culling would be the most appropriate strategy from a control perspective provided the high economic and social costs of this approach were also considered.
For HPAI, for which there is no known long-term carrier state (on an individual bird basis) and limited duration of survival of the virus outside the host, especially in tropical and sub-tropical areas, or on certain soil types, it is highly likely that outbreaks in areas with low concentrations of poultry and limited poultry movement will be self-limiting (as seen in several African countries and predicted in modelling studies in the UK) – a factor that should be taken into account when planning responses to outbreaks, especially if wide-area culling is being considered.
These studies and field experiences demonstrate that even with stamping out, there are various options to consider and that the method used should be based on the nature of the poultry sector in the infected area and the extent of spread of the virus. Further studies are needed to determine the most appropriate and cost-effective strategies for disease control and prevention especially in places at high risk of disease outbreaks (such as those bordering infected countries) where disease has recurred over several years as a result of re-incursion of viruses and where there is often a time lag between virus incursion and disease reports (e.g. West Bengal). At present, wide-area culling is the method of choice in India but faces many problems.
Some of the potential negative effects of wide-area stamping out that have been observed include resistance from farmers and movement/sale of poultry ahead of culling operations, animal welfare issues when culling poultry in remote locations or poor countries and the cost (both direct costs and indirect costs to those affected) as was the case in the early response in Vietnam where some 40 million poultry were culled, especially if the culling programme does not result in sustained freedom from infection because not all infected flocks are detected.[23, 45]
These issues are compounded if compensation for affected poultry farmers is not available or does not cover a significant portion of the value of culled birds. In all cases where stamping out is applied as a control measure current recommendations state that compensation should be paid to affected farmers to minimise the losses following reporting of disease. Availability of compensation does not guarantee all cases will be reported as has been demonstrated in a number of countries.[22, 47] Surveys of farmers and traders in developing countries also demonstrate this effect but field observations suggest that availability of adequate levels of compensation probably results in better reporting than in places where no or poor compensation is given. Some countries claim they do not have the resources to pay compensation or pay at levels that are too low to stimulate disease reports, which means other methods need to be found to encourage reports, including training and support of community-based animal health workers to detect and report disease, which is not always successful in improving disease reporting. Adverse effects of compensation (including corrupt practices) observed in other programmes have also influenced at least one country in its decision not to pay compensation for avian influenza. Most observations on compensation, including suggestions regarding appropriate levels of compensation, have not been subjected to scientific studies quantifying the effectiveness of compensation as a driver of reporting or the adverse effects of a lack of or too little compensation on disease reporting. Experiences with compensation from Nigeria, where (eventually) high-level compensation was apparently paid and virus was eliminated, warrant closer examination to assess whether the link was causative, although one modelling study suggests that the low transmission rate from infected sites may also be relevant to the course of the outbreak. In Turkey, contract farmers working for integrated companies were not covered by compensation programmes and suffered considerable losses, demonstrating that even when compensation is available, it may not be paid to those who grow the poultry, reducing its effectiveness as a tool for encouraging disease reporting.
Ultimately, the success of stamping out depends on early detection and elimination of infected animals. It will not be successful in places with high poultry density if disease reporting and surveillance systems are not sufficiently robust to detect all cases when they first occur, as is the case in most of the countries where influenza A (H5N1) viruses are endemic in poultry, leading to ‘harvesting’ of cases. The key factors are the incentives/disincentives for reporting by farmers, the quality of animal health services and also the nature of the disease (in particular, whether or not it is apparent to farmers or animal health workers that their poultry may have avian influenza – which is not necessarily the case with LPAI, or with HPAI in ducks). Unless active surveillance programmes are in place most outbreaks of LPAI will not be detected.[53, 54] Even H5N1 HPAI viruses may not be detected without active surveillance in markets and domestic water fowl populations as is the case in China where no outbreaks of disease in poultry due to H5N1 HPAI virus have been recorded at times when virus was still being detected in markets via active surveillance.
Vaccination can also complicate surveillance and therefore it is necessary to build appropriate surveillance programmes to detect virus circulation in places where vaccines are used. In places with mass vaccination programmes involving millions of poultry, such as the ones that have been used in China and Vietnam, resources are not available to test every flock for evidence of infection but sufficient samples should be collected (often through targeted surveillance) to ensure viruses circulating in vaccinated poultry are detected and characterised.
As with control measures for H5N1 HPAI, surveillance systems for this disease vary from place to place. Recommendations on influenza surveillance for poultry have been made with the design of surveillance programmes depending on the objectives and the resources available. Much emphasis has been placed on participatory surveillance and response in Indonesia for H5N1 HPAI, whereas more traditional methods of disease reporting and surveillance are used in China and Vietnam. The Indonesian system appears to have provided better information on disease prevalence at the village level than the systems in China and Vietnam but it is not yet clear whether the overall benefits, in terms of disease control, outweigh the cost of obtaining the information about this disease, which, despite the regular detection and response, is proving difficult to eliminate.
Stamping out can be used for LPAI as it is with HPAI but is usually confined to outbreaks caused by viruses defined as low pathogenicity notifiable avian influenza (LPNAI) – that is, viruses of the H5 and H7 subtype that have not acquired (but have the potential to acquire) characteristics of high pathogenicity viruses. Alternatives to whole farm depopulation have been used in the United States for some outbreaks of LPNAI, including the use of vaccination and controlled marketing in which birds are sold to slaughter once clinical signs have abated and viral shedding is at a low level. Significant cost savings occurred as a result of implementation of modified approaches with a 10:1 cost benefit calculated for a programme incorporating vaccination over total depopulation for one large layer farm complex infected with an LPNAI virus. This is but one example of cases where alternative approaches to classical stamping out have been used to eliminate LPAI from poultry flocks. Vaccination has also been used in Italy for similar purposes for the elimination of LPNAI.
At present, few farms are depopulated following infection with influenza viruses of the H9N2 subtype, which is endemic in poultry across much of Asia and the Middle East. Some LPAI viruses are poorly transmissible between poultry; others such as H9N2 viruses are readily transmitted with some strains capable of spread via the airborne route, a factor that should influence the design of control and preventive measures for this disease, including stamping out.
Vaccination of poultry against avian influenza has the capacity to increase resistance to infection, to protect poultry from clinical disease and to reduce shedding of virus if vaccinated poultry become infected. Numerous studies, reviewed elsewhere, have demonstrated that vaccines under experimental conditions can prevent transmission of virus. This review also highlighted many of the gaps in knowledge on vaccination programmes and discussed the ‘science’ and ‘art’ of vaccination, both of which need to be considered when planning and implementing vaccination programmes.
Well-managed vaccination of poultry can reduce the risk to humans by reducing the quantity of circulating virus. Used alone, vaccination will not normally eliminate HPAI but it can be used as one of the tools for doing so, as was the case in Mexico (H5N2 HPAI and H7N3 HPAI) and Hong Kong in 2002 (H5N1 HPAI).
In most outbreaks in newly infected countries, vaccination against HPAI probably has a limited role to play except to protect valuable birds or those at high risk of infection such as poultry reared outdoors, and, with few exceptions, has not been used as a measure of first choice. Implementing emergency vaccination requires plans and resources (including suitable vaccines, which could be made available from vaccine banks) to be in place well before an outbreak occurs. Modelling conducted in Australia on simulated outbreaks in the intensive poultry sector suggests that emergency vaccination would have limited benefits compared with other strategies at least for moderate-sized outbreaks. Modelling of simulated outbreaks in the UK also suggests emergency vaccination would not be required to control most outbreaks of HPAI or if so would be used in conjunction with wide-area culling. The experiences from the H7N3 outbreak in Mexico in 2012 in which vaccination was used to assist in disease control warrant further investigation.
If countries with endemic infection in poultry see few prospects of virus elimination in the short term, it has been proposed that they should assess whether and how vaccination can play a role in minimising the damage done by the virus, including reducing the probability of human infections, while other measures to control and prevent the disease are gradually introduced. This process involves questions regarding the logistics of vaccination delivery such as the capacity to deliver vaccine of appropriate quality to the places where and when it is needed, the cost of the programme for the population to be vaccinated (commercial or backyard) and issues related to rates of turnover of poultry and effects on population immunity.
A number of countries with endemic infection in poultry have concluded that vaccination has a role to play and it has been used as one of the measures for disease control and prevention in China and Vietnam (where large-scale government sponsored programmes have been implemented but have been scaled back in 2011–2012) and also Indonesia and Egypt (where much of the vaccination has been done by the private sector). Bangladesh is due to commence trials on vaccination in late 2012.
Not all vaccination programmes have been implemented well, and the lessons from these programmes need to be assessed when considering vaccination as part of a control or preventive programme. Targeting of vaccination is recommended and has already been used in Vietnam where vaccination has focused on areas perceived to be at higher risk, including the Mekong and Red River deltas, and in China where export farms implementing high-level biosecurity measures do not use vaccination against H5N1 HPAI viruses. Studies on alternate vaccination strategies for Vietnam have been conducted in which comparisons were made between different methods to improve targeting of vaccination.
Many factors influence the quality of the immune response generated by vaccines, including the timing of vaccination (affected by pre-existing maternally derived antibodies),[68-70] the quality of vaccines (antigenic match to circulating strains, antigen content, the quality of the adjuvant and vaccine storage),[70-72] the number of doses, concurrent diseases, the species or strain of bird being vaccinated,[75, 76] and, perhaps most important of all, whether or not poultry are actually vaccinated (failure to vaccinate rather than vaccine failure).
Antigenically variant avian influenza strains have emerged, and it is possible that vaccination is playing a role in this process.[78, 79] Vaccination programmes should be designed to stimulate a strong immune response. However, if vaccines are used widely, it can be difficult to develop and maintain high-level immunity in all vaccinated flocks. Antigenic variation in avian viruses has implications for human pandemic preparedness in selecting strains for candidate human pandemic vaccines, a process that is already in place and supported by provision of data by the OIE Food and Agriculture Organization of the UN (FAO) global network of expertise on animal influenza (OFFLU) on avian isolates derived from disease investigations and surveillance programmes.
There are merits in developing improved vaccines and vaccination programmes, including vaccines and programmes that stimulate both arms of the immune system (humoral and cell-mediated) to broaden protection, as is the case with many other avian vaccination programmes. New vectored vaccines for H5N1 HPAI viruses under development potentially offer advantages over existing vaccines containing killed antigen or can be used in combination with them,[81, 82] but their benefits need to be assessed under field conditions, including likely uptake of the vaccines by producers. Other vector vaccines (including pox virus and paramyxovirus) have been used but have not gained traction for use against H5N1 HPAI.
Maintaining mass vaccination campaigns is expensive.[84, 85] The cost has to be weighed against that of other control and prevention options as well as the extent of reduction of risk to the human population of a human influenza pandemic (brought about because of transmission of virus from poultry to humans and subsequent adaptation in humans). The economics of large-scale vaccination have been reviewed. One study on vaccination in northern Vietnam reported very low rates of seroconversion in vaccinated small flocks but the rates reported were much lower than those reported in post-vaccination surveillance conducted by national veterinary authorities after the first and second rounds of vaccination.
It has been suggested that vaccination resulted in endemic infection in the places where it has been used but, in fact, vaccination was a response to endemic infection or high risk of virus incursion into farms. In China and Vietnam, it has not been possible to determine the precise role of vaccination in reducing the threat to humans. It appears that the risk has fallen over time given the reduction in the number of reported human cases but a causal link to vaccination has not been established. In Vietnam, the introduction of vaccination in 2005, along with other measures, was followed by a period in which no new poultry outbreaks were reported, no peak of cases occurred during the Tet festival in 2006 and no human cases were reported for over 12 months. At least one modelling study (based on reported cases) suggests some positive effects in Vietnam on reduction of transmission of virus in poultry between communes, providing indirect evidence of the benefit for humans.
The absence of virus-positive poultry in Hong Kong retail markets after full implementation of vaccination of poultry destined for these markets (other than one antigenic variant strain in 2008) also provides support for the benefits of a well-managed vaccination programme in reducing exposure of humans to influenza A(H5N1) viruses. The introduction of other measures to markets including a single rest day had not prevented reinfection of these markets.[20, 73]
The nature of vaccination programmes also needs to be considered when assessing effectiveness of vaccination. Maintaining high-level flock immunity is difficult in places with high rates of turnover of poultry. However, it may be possible to aim for high levels of immunity at certain times of the year just prior to high-risk periods (which was the basis for the initial mass campaign in Vietnam in 2005 given the seasonal peaks of occurrence in the period around the Tet festival in 2004 and 2005). More work is needed to understand the effectiveness and risks of such targeted strategies especially the effect of waning immunity on selection for antigenic variants if the programme leads to infection in sub-optimally immune birds as their immunity wanes.
As HPAI (regardless of the subtype involved) is still regarded as an eradicable disease and has been eliminated from poultry in most countries when it occurred, long-term vaccination without an exit strategy is not recommended by FAO and OIE. Nevertheless, it is evident that vaccination against H5N1 HPAI will be used as part of the preventive programme for this particular disease for some time in some countries with endemic infection in poultry and those where the risk of infection remains high. Such long-term use of vaccines does not necessarily signal acceptance of endemic infection. Rather, it is a reflection of the time required and difficulties encountered in making the necessary changes to production and marketing systems and improvements to animal health and production services regionally that are needed for further progress towards elimination of the virus. These other factors probably contributed to the disease becoming endemic in the first place; ongoing vaccination as the main control measure in the face of endemic infection, without other changes and measures will not result in virus elimination.
Vaccination against HPAI removes the signal of clinical disease in poultry that allows detection of infection in chickens (less so in ducks where, for some strains and older birds, infection can already be subclinical without vaccination). This is counterbalanced by the likely reduction in virus excretion if well-vaccinated poultry are subsequently infected, which should reduce the risk to humans. In Cambodia where avian influenza vaccine is not used routinely in poultry in rural areas, disease in humans in 2011 was usually preceded by deaths of poultry in the village suggesting it is not the absence of the signal of poultry mortality that is the main issue but rather failure to report disease in poultry when it occurs and inappropriate handling of dead birds. Potential public health disadvantages in using vaccines could arise in situations where vaccination removes the signal of clinical disease but does not reduce virus shedding in poultry subsequently exposed to the virus, as can occur in ducks given a single dose of vaccine.
Vaccines are used widely to reduce the effects of H9N2 avian influenza in poultry flocks in many parts of Asia and the Middle East. Vaccines are also used for LPNAI in Mexico and have been used successfully to control LPNAI outbreaks in Italy. Vaccines were also used successfully as part of the control programmes in large farms in the United States with LPNAI that were not fully depopulated as described in the previous section on stamping out.
Alternative methods for raising resistance of poultry to influenza viruses are also being explored with development of transgenic chickens. While the initial results of one trial were interesting (the genetic modification did not prevent disease in experimentally infected birds but onward transmission did not occur), much more work and societal support for such measures are needed if they are to be adopted in the future.
Biosecurity measures introduced to farms or in markets to reduce the likelihood of introduction of avian influenza viruses can markedly reduce the risk of infection of poultry and provide a return on investment. A key constraint is that the measures must be cost-effective for the production system and producer.[32, 90] Most small village flocks in Asia are not confined, despite some advice to the contrary, because once the birds are confined it costs more to house and feed them. The appeal of scavenging poultry to villagers is that they can be reared with virtually no financial input. This demonstrates that the measures proposed for small-scale poultry producers must be practical and affordable, focusing in particular on behavioural change and simple, cost-effective measures. Egypt represents a special case because most smallholder poultry are reared in buildings or on rooftops rather than as scavenging flocks.
For some production systems, such as free-grazing ducks, only marginal improvements can be made to biosecurity, which means that other ways to protect these poultry must be found such as better controls on movement (not always easy to implement) and vaccination, especially if high-level immunity can be generated at an early age.
Markets and traders’ yards are considered important points in market chains for virus transmission and persistence and for human infections. Improvements in hygiene and changes in management practices such as market rest days or bans on overnight keeping can help to reduce the likelihood of infection occurring and persisting, but unless strict controls are placed on sources of poultry, reinfection will occur. The appropriate number of rest days depends in part on attitude to risk. In one study in Hong Kong, using H9N2 virus as the marker, two rest days were shown to offer little or no improvement to a single rest day. Banning of overnight keeping is effective, preventing markets from becoming permanently infected given the duration of stay is less than the incubation period of the virus. However, this requires all birds in stalls to be sold/dressed on a daily basis and potentially increases the financial risk for traders (who are paid substantially more for live than dressed poultry) especially if fluctuations in demand are difficult to predict. The experiences from Hong Kong SAR are noteworthy here with most stall holders opting out of the live poultry trade when this measure was introduced albeit after being provided with ex gratia payment.
Biosecurity measures should be based on the assessment of each of the potential pathways for virus introduction along production and marketing chains to ensure that appropriate, cost-effective measures are in place to minimise the risk posed along each pathway. The main pathways for introduction of influenza viruses are live poultry, wild birds, feed, water, rodents and other pests, people, vehicles and other fomites and possibly local airborne spread. A number of case–control studies have identified specific risk factors for virus entry to farms.[95-99] The main risk factors identified and likely mode of entry of virus differ from place to place, but broadly speaking these studies have shown that anthropogenic spread is an important means of transmission for HPAI, confirming what has been known about avian influenza for many years. Measures also need to be introduced to minimise contact of poultry with wild birds so as to prevent infection with influenza (and other) viruses.
Field observations and assessments of biosecurity measures on farms demonstrate that although some farms have very high-level biosecurity measures in place, there is still considerable work to be carried out to reach standards that would prevent virus from entering many other farms.
The main objective for most poultry owners is to prevent virus from gaining entry to farms. Nevertheless, farmers are also advised to implement cost-effective measures to limit onward transmission of virus within and beyond infected farms once disease occurs. This covers items such as handling dead poultry, manure and waste water all of which have been identified as important for onward transmission. Many of the measures required to prevent avian influenza are based on changes to management procedures rather than just improving facilities. Any recommended changes in practices must be acceptable to farmers otherwise they will not be implemented.[32, 94]
Communication campaigns have been used to modify behaviour and to reduce high-risk practices such as dressing and preparing sick or dead poultry for consumption. The campaigns have increased awareness and resulted in some behavioural change[48, 100] but they have not always been successful in having long-term effects on behaviour, as seen with ongoing human cases in Cambodia in 2011, many of which were associated with preparation of sick or dead poultry for food. Many factors, including poverty, influence the willingness to report disease in poultry and to change behaviour.
Many countries have implemented routine disinfection programmes for control and prevention of avian influenza and the use of these chemicals forms part of outbreak management. It is evident from field observations that there has been considerable misuse of these chemicals. Cleaning is not always used as a preliminary step prior to disinfection, and many disinfectants are applied to areas with high loads of organic matter that reduces the efficacy of the disinfectants. In other cases, contact times are too short for virus inactivation. Formal studies have not been conducted to evaluate the cost-effectiveness of disinfection programmes applied in and around villages for the prevention of avian influenza. In addition, experimental studies conducted in Cambodia suggest that virus survival in sandy soils typical of that country is short, which may have implications on the need for use of disinfectants.
Movement management has been applied around outbreak sites and at key points within and between countries, with variable effects, given that movement controls have not stopped the transboundary spread of this disease. Movement management is an essential component of all avian influenza control and preventive programmes but traditional cross-border trade routes and poultry smuggling reduce their effectiveness. Again, few of the movement controls in place have been assessed for the benefits they provide. The measures recommended in the OIE terrestrial code for international trade, if implemented correctly, would be expected to prevent incursions of virus through legal trade. Thailand's movement controls for grazing ducks within the country may provide lessons for other countries looking at improving controls but the numbers of ducks involved there is far lower than in some other countries in the region.
Major changes have been introduced to the methods of sale of poultry in a number of places. Several large cities have banned the sale of live poultry in markets (e.g. Beijing, Ho Chi Minh City) or placed very strict controls on the manner in which live poultry can be sold (e.g. Hong Kong SAR). These measures reduce the likelihood of contact between infected poultry and humans and it is pertinent that no new locally acquired human cases have been detected in Ho Chi Minh City and Hong Kong since they were implemented (although they were not the only measures implemented). The main risk associated with changes to the way poultry is sold is that unmet demand for live poultry may result in illegal sales of live birds in uncontrolled premises, requiring additional enforcement.