Ag department criticized for bird flu plan

Senators criticize planned voluntary bird flu testing

By Libby Quaid
Associated Press

Washington | Senators on Friday criticized the Agriculture Department's planning for deadly bird flu, saying the voluntary nature of its testing program threatens the U.S. poultry industry.

At issue is a federal audit that found the government lacks a comprehensive plan for testing and monitoring bird flu in commercial poultry. The department says it will have a plan in place by October.

"It is surprising that USDA does not have a program that monitors and collects data on what testing is taking place," the senators wrote in a letter to Agriculture Secretary Mike Johanns.

"We are deeply concerned that the agency has waited until this year to begin to develop a comprehensive surveillance plan for avian influenza, which will not be complete until October," wrote the group, which includes Sen. Tom Harkin, D-Iowa.

The group includes four other Democrats - Sens. Harry Reid of Nevada, Barack Obama of Illinois and Hillary Clinton and Charles Schumer of New York - and one Republican, Sen. Charles Grassley of Iowa.

Wild birds in Thai consumed; possible H5N1 in human eaters

Bangkok - Two Thai men have been hospitalized for showing symptoms similar to bird flu after consuming wildfowl in Uttaradit - one of seven provinces in the country's 'red zone' for the animal pandemic, reports said on Sunday.

Uttaradit chief medical officer Boonriang Chuchaisaengrat said further tests were needed to establish whether an unidentified 67-year-old man and his 35-year old son-in-law had contracted avian influenza or not, reported the Thai News Agency.

The two men had reportedly developed flu-like symptoms after eating a wild bird, believed to be a spotted dove, in Uttaradit.

Uttaradit is one of seven central and northern provinces that were recently classified as a 'red zone' for avian influenza, although agriculture and health authorities have thus far denied any confirmed cases of a reappearance of the animal pandemic in the area.

There have been news reports of mysterious mass deaths of the poultry in the provinces.

Bird flu was first confirmed in Thailand in late 2003, after months of what was deemed a government coverup of outbreaks in the country's massive commercial poultry industry, once a major export earner.

Thailand has claimed to be bird flu free for most of this year, and if its status is confirmed without further outbreaks the country may soon resume exports of uncooked chicken meat.

Since bird flu was first detected in the kingdom there have been 19 confirmed cases of the H5eN1 virus among humans, 13 of whom have died.

The last confirmed case of a human infection with avian influenza was a 7-year-old boy from Kanchanaburi Province, who developed symptoms on October 16 and was hospitalized on 19 October. He recovered.

© 2006 dpa - Deutsche Presse-Agentur

Healthcare workers and pandemic flu

Volume 12, Number 8–August 2006

Policy Review

Virulent Epidemics and Scope of Healthcare Workers' Duty of Care

Daniel K. Sokol*
*Imperial College, London, United Kingdom

Suggested citation for this article

The phrase "duty of care" is, at best, too vague and, at worst, ethically dangerous. The nature and scope of the duty need to be determined, and conflicting duties must be recognized and acknowledged. Duty of care is neither fixed nor absolute but heavily dependent on context. The normal risk level of the working environment, the healthcare worker's specialty, the likely harm and benefits of treatment, and the competing obligations deriving from the worker's multiple roles will all influence the limits of the duty of care. As experts anticipate the arrival of an avian influenza pandemic in humans, discussion of this matter is urgently needed.

Epidemiologists are warning against an impending pandemic of avian influenza that could kill several million people (1). This possibility raises an urgent and thorny ethical question: Are healthcare professionals obligated to care for patients during virulent epidemics of infectious disease?

Duty of Care

Duty of care, in the medical context, is often invoked as a sort of quasi-biblical commandment, akin to "do not lie" or "do not murder." In a document submitted to the Severe Acute Respiratory Syndrome (SARS) Expert Panel Secretariat, Godkin and Markwell suggest that policy guidelines on the duty of care (which they term duty to care) should state that healthcare professionals' duty to care extends to a public health emergency in outbreak conditions (2). The authors however suggest that healthcare employers have a set of reciprocal responsibilities toward their staffs, which include duties to inform, protect, and support healthcare personnel. Singer et al., in an article on the ethical issues raised by SARS in Toronto, briefly discuss the duty to care before concluding that the 9 authors "could not reach consensus on the issue of duty of care, particularly regarding the extent to which healthcare workers are obligated to risk their lives in delivering clinical care" (3). The term "duty of care" (which I take to be synonymous with duty to care) is, at best, too vague and, at worst, ethically dangerous. For these reasons, the phrase should be modified in favor of more specific descriptions of the obligations of healthcare workers.

Special Obligation of Doctors to Benefit Their Patients

By virtue of their profession, doctors and nurses have more stringent obligations of beneficence than most. They have obligations to a specified group of persons (their patients) that nonmedical personnel have no obligation to help. The term "duty of care" refers to these special obligations. In its bare form, however, the phrase gives no indication of the precise nature of the duty, nor of its limits. Its definitional vagueness, combined with its rhetorical appeal, may be used to justify actions without the need for rational deliberation. During the SARS outbreaks in Toronto, the phrase was often used as a self-standing argument for active involvement on the part of medical staff, without any critical examination of its meaning. Used in this manner, the term may become a subtle instrument of intimidation, pressuring healthcare workers into working in circumstances that they consider morally, psychologically, or physically unacceptable. The phrase duty of care can thus be ethically dangerous by giving the illusion of legitimate moral justification.

To be of any use, the phrase needs to be fleshed out. Are there limits to the duty? Should doctors do everything in their power to benefit their patients? The answer, surely, is no. Doctors are under no moral obligation to donate one of their kidneys to one of their patients, for example. They may, of course, choose to do so, but their act would exceed the demands of everyday morality. What distinguishes normal duty from acting beyond the call of duty, however, is not always clear-cut; the boundary between the 2 categories is fuzzy (4).

Contingency of the Limits of Duty of Care

Defining the limits of the duty of care is a daunting task, strewn with philosophical and logistical difficulties. As the example of the kidney-giving doctors shows, the duty is not absolute but, rather, constrained by several factors. First, the limits of the duty should be a function of the normal risk level. A doctor practicing in Kinshasa, Democratic Republic of Congo (DRC), for instance, is going to incur more risk than a doctor in rural Dorset, England. The diseases are many and the facilities few in DRC. Every nurse or doctor, by accepting a post, is usually aware of the perils of treating infected patients. The appearance of an exotic, highly virulent disease, however, challenges healthcare workers to question their interpretation of the duty of care, in particular, its limits. This challenge was apparent both in the HIV/AIDS epidemics of the 1980s in the United States and in the 2003 SARS outbreaks in Toronto, in which doctors and nurses refused to treat afflicted patients on the grounds that they presented too great a danger (2,5). This phenomenon is also likely to occur if the anticipated avian influenza epidemic affects Western hospitals. In light of these historical precedents, hospitals may want to inform prospective staff members of what is expected in crisis situations before, rather than in the midst of, an emergency. By using comparisons and statistics, hospitals could indicate the sorts of risks healthcare staff are expected to handle.

Another factor in defining acceptable risk levels relates to the healthcare worker's specialty. Within the same hospital, an emergency care physician, as a first responder to many critically ill or injured persons, is obviously more at risk than, for example, a dermatologist. By entering into a specialty, doctors implicitly consent to a range of risks and responsibilities associated with the job. The outer limit of acceptable personal risk will fall further along the continuum of risk for some specialists (e.g., infectious disease physicians) than for others (e.g., dermatologists or rheumatologists). During the SARS outbreaks in Toronto, the persons most at risk were nurses and infectious diseases (ID) specialists. As a result of their specialist training, they may have felt a stronger obligation to participate than doctors in other areas of medicine.

Doctors as Multiple Agents

Doctors, although they belong to their own professional community and adhere to its set of rules, are also part of the broader community and therefore subject to the same rights and duties as other members. The 2 spheres of obligation, professional and personal, are both separate and overlapping. They are separate in that the obligations of doctors toward their patients give them rights that nonmedical members of the society do not possess, such as opening someone's abdomen to remove an appendix. The spheres are overlapping, however, in that their role as doctors does not completely absolve their responsibilities as members of the broader community. The immunity from sanction is specific, not general. A gynecologist may legitimately examine intimate parts of his or her patient but cannot drive beyond the speed limit or steal apples from the market stall. With the acquisition of additional duties and rights conferred by the profession, the doctor also agrees to relinquish certain rights enjoyed by others. By entering into the profession, a doctor agrees not only to abide by new rules but also to accept dangers that would be unacceptable to many (e.g., performing a delicate, invasive procedure on a patient with hepatitis or HIV/AIDS).

In times of crisis, the duties deriving from doctors' multiple roles may come into conflict. Doctors, for instance, may have a duty to care for their SARS or avian influenza–infected patients as well as a duty to care for their own children by protecting them (and hence themselves) from infection. So a further problem with the duty to care, aside from its vagueness, is that it fails to consider the holder of the duty as a multiple agent belonging to a broader community. Doctors, in such situations, play several incompatible roles—doctor, spouse, parent, for example—and they must deal with them as best they can. The limits of the duty of care are thus also defined by the strengths of competing rights and duties.

Virtues of Patients and Their Duty of Care

Whereas much has been written on what makes a good doctor, scant attention has been devoted to the good patient (6,7). Pellegrino and Thomasma, in For the Patient's Good, devote a chapter to the "good patient" (8). "Patients," they write, "must relate to physicians in all of the virtuous ways that govern human interrelationships and social conduct" (8). The authors identify 4 key virtues for the good patient: truthfulness, compliance, tolerance, and trust. The virtue most pertinent to this discussion is tolerance. In their examination of tolerance, Pellegrino and Thomasma mention the patients' need to understand the limitations and fallibility of medicine and to care for the well-being of their fellow patients (8).

The virtue of tolerance should also require patients to acknowledge healthcare workers' plurality of roles, as well as their fears and concerns in the face of severe risk. If these fears are well founded and reach such a level that medical staff are worried for their life or that of their loved ones, the virtuous patient ought to allow them to step down from their role as caregivers. In such cases, insisting that they continue in this role would reflect a lack of compassion and understanding. Patients should be entitled to ask for a replacement who is less anxious or prone to panic, but they cannot force other persons to undergo extreme stress against their wishes.

When a physician visited the 1995 Ebola virus outbreak in Kikwit (DRC), he found 30 dying patients in an abandoned hospital, left to care for themselves amid rotting corpses, sometimes in the same bed (9). Was the last doctor justified in leaving the patients, or should he or she have been obliged to single-handedly treat the highly and dangerously infectious Ebola patients? The answer depends, at least in part, on the actual risk to the doctor and the potential benefits (including the alleviation of pain and distress) that his or her presence will bring to the patients. If the actual risk for serious illness or death for the doctor is low and the benefits of treatment substantial, then he or she may have an obligation to remain. If, however, the lack of protective equipment means that the chances of infection are high and no, or trivially small, benefits will result for the patients (as is often the case with Ebola), then the doctor may justifiably abandon the doomed patients. Virtuous patients, aware of the high risk and the futility of treatment, would not force a doctor to care for them in such circumstances. Patients too have a duty to care for healthcare workers. Part of this duty is not to require doctors to transcend the bounds of reasonable risk during treatment and to respect and acknowledge their roles outside the realm of medicine.

As potential participants in the drama and as holders of a duty of care toward healthcare workers, the general public also should be involved in setting limits to duty. Some form of dialogue between the public and the medical profession, through the media, public consultations, and educational establishments, could help establish a mutually acceptable set of limits.

Impact on Patient Trust

The justified abandonment of patients by doctors arguably will result in the harm or even death of these patients. Moreover, public trust in doctors will diminish as persons realize that they, like the 30 forsaken Ebola patients at Kikwit General Hospital, might be left on their own as soon as the risk reaches a certain level. The patients at Kikwit died alone, abandoned by both medical staff and their own frightened relatives. So tragic is the situation that it seems counterintuitive to justify the actions of the nurses and doctors. Yet, before passing judgment, comparing this situation with another hypothetical situation may be useful.

If a swimmer in an isolated but supervised beach starts to drown 50 meters from the shore, the lifeguard may reasonably be expected to attempt a rescue. This, after all, is the lifeguard's duty as a qualified professional. If, however, the person is drowning 2 miles out and is surrounded by a school of hungry, man-eating sharks, then one cannot expect the solitary lifeguard to dive among the sharks to save the swimmer, even if that means the swimmer will certainly die and even if the lifeguard has a small chance of saving him or her (at great personal risk).

The lifeguard cannot be criticized for not interfering, even though his or her prima facie duty is to rescue drowning persons. Likewise, the fact that doctors can, in exceptional circumstances, refuse to treat patients does not necessarily entail a moral wrong, no matter how serious the consequences to the abandoned patients. As long as patients hold realistic expectations of the limits of doctors' duty of care, no trust should be lost when these limits are transgressed.

Urgent Need

In the last 20 years, various outbreaks of severe infectious diseases, from Ebola virus infection to SARS, have highlighted the need for a more precise account of the duties and obligations of healthcare professionals. The impending avian influenza epidemic makes such an account urgent. The concept of duty of care, in its bare form, is too vague to be helpful. Its limits are not fixed, but contingent on various factors, from the working environment's normal risk level to the healthcare worker's specialty and the range of other obligations that derive from his or her multiple roles. To clarify this overlooked topic, empirical social science research should be conducted to illuminate the views and reasoning of physicians, patients, and members of the public on the limits of the duty of care. Philosophical reflection on the issue as well would do much to clarify this overlooked topic. As dramatic as it may sound, delineating the limits of the duty of care may prevent large numbers of doctors from abandoning their patients in a crisis. Such abandonment has happened in the past and may occur again.

In light of the potentially catastrophic impact of avian influenza on human health and economic well-being, this topic should engender a burst of activity and debate in hospitals, universities, and medical journals. We should explore not only the nebulous limits of the duty of care but also infection control measures, staff training and involvement, the role of medical students and volunteers, the triaging of incoming patients, and the logistics of treatment, depending on the severity of the epidemic, as well as the lessons learned from past epidemics. However difficult the task, these issues should best be tackled now, in times of relative calm, rather than in times of pandemic turbulence.

Acknowledgments

I thank Raanan Gillon, Anna Smajdor, and the 2 anonymous reviewers for their comments on earlier drafts.

Dr Sokol is a researcher in medical ethics at Imperial College, London. His primary interest is in the ethics of the doctor-patient relationship.

References

1. British Broadcasting Company News Online. Bird flu "could kill 150m people." 2005 Sep 15 [cited 2006 Jun 5]. Available from http://news.bbc.co.uk/2/hi/asia-pacific/4292426.stm
2. Godkin D, Markwell H. The duty to care of healthcare professionals: ethical issues and guidelines for policy development. Toronto: Joint Center for Bioethics, University of Toronto; 2003.
3. Singer P, Benatar S, Bernstein M, Daar AS, Dickens BM, MacRae SK, et al. Ethics and SARS: lessons from Toronto. BMJ. 2003;327:1342–4.
4. Heyd D. Supererogation: its status in ethical theory. Cambridge (UK): Cambridge University Press; 2002.
5. Zuger A, Miles S. Physicians, AIDS, and occupational risk. Historic traditions and ethical obligations. JAMA. 1987;258:1924–8.
6. Sokol D. How (not) to be a good patient. J Med Ethics. 2004;6:612.
7. Campbell A, Swift T. What does it mean to be a virtuous patient? Virtue from the patient's perspective. Scottish Journal of Healthcare Chaplaincy. 2002;5:29–35.
8. Pellegrino E, Thomasma D. For the patient's good. New York: Oxford University Press; 1988.
9. Virus. British Broadcasting Company Radio. 1999 Mar 3.

Thai birds had H5N1

Birds in Phichit has bird flu virus

The deadly birdflu virus has struck for the first time this year. Officials admitted on Monday the disease had killed birds in Phichit.

Agriculture Minister Sudarat Keyuraphan said the outbreak had been contained.

After weeks of reports of susฌpected birdflu deaths in poultry in several areas, livestock authorities announced yesterday tests had come back positive for the virus.

Laboratory results found at least 20 samples taken from dead fightฌing birds in Phichit were positive for bird flu, Sudarat said in a stateฌment.

The bird's owners were free of the virus, she said.

Quarantine had been imposed within a radius of one kilometre from where the birds died. The transport of all birds had been proฌhibited.

The ministry admitted the virus had been detected in samples of imported chicken.

Thailand immediately banned the import of all forms of poultry, Sudarat.

The Health Ministry and Phichit officials were stepping up checks for flu symptoms in people, Disease Control Department director general Dr Tawat Suntharacharn said.

Teams of epidemiologists had been dispatched to Phichit to assist local disease experts.

Fifteen suspected birdflu patients were taken off the watch list yesterday after tests proved negative. Two of those were from Phichit, said Dr Paijit Warachit, head of the Medical Sciences Department.

Meanwhile, Phitsanulok has reported a fiveyearold boy may be suffering from the virus. Uttaradit has three new suspected cases.

Both provinces continue to report unexplained poultry deaths.

The Nation

CIDRAP reports/study

Volume 12, Number 9–September 2006

Synopsis

Control of Avian Influenza in Poultry

Ilaria Capua* and Stefano Marangon*
*Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Padova, Italy

Suggested citation for this article

Avian influenza, listed by the World Organization for Animal Health (OIE), has become a disease of great importance for animal and human health. Several aspects of the disease lack scientific information, which has hampered the management of some recent crises. Millions of animals have died, and concern is growing over the loss of human lives and management of the pandemic potential. On the basis of data generated in recent outbreaks and in light of new OIE regulations and maintenance of animal welfare, we review the available control methods for avian influenza infections in poultry, from stamping out to prevention through emergency and prophylactic vaccination.

Avian influenza (AI), which emerged from the animal reservoir, represents one of the greatest recent concerns for public health. Compared with the number reported for the past 40 years, the number of outbreaks of AI in poultry has increased sharply during the past 5 years. The number of birds involved in AI outbreaks has increased 100-fold, from 23 million from 1959 through 1998 to >200 million from 1999 through 2005 (1). Since the late 1990s, AI infections have assumed a completely different profile in the veterinary and medical scientific communities. Some recent outbreaks have been minor, but other epidemics, such as the Italian 1999–2000, the Dutch 2003, the Canadian 2004, and the ongoing Eurasian, have been more serious. They have led to devastating consequences for the poultry industry, negative repercussions on public opinion, and, in some instances, created major human health issues, including the risk of generating a new pandemic virus for humans through an avian-human link.

Influenza viruses are segmented, negative-strand RNA viruses that are placed in the family Orthomyxoviridae in 3 genera: Influenzavirus A, B, and C. Influenza A viruses are the only type reported to cause natural infections of birds and are further divided into subtypes according to antigenic characteristics of the surface glycoproteins hemagglutinin (H) and neuraminidase (N). At present, 16 hemagglutinin subtypes (H1–H16) and 9 neuraminidase subtypes (N1–N9) have been identified. Each virus has one H and one N antigen, apparently in any combination; all subtypes and most possible combinations have been isolated from avian species.

Influenza A viruses that infect poultry can be divided into 2 distinct groups according to the severity of disease they cause. The most virulent viruses cause highly pathogenic avian influenza (HPAI), a systemic infection in which death rates for some susceptible species may be as high as 100%. These viruses have thus far been restricted to strains that belong to the H5 and H7 subtypes and have a multibasic cleavage site in the precursor of the hemagglutinin molecule. HPAI is a lethal infection in certain domestic birds (e.g., chickens and turkeys) and has a variable clinical effect (may or may not cause clinical signs and death) in domestic waterfowl and wild birds. The potential role of wild birds and waterfowl as reservoirs of infection by HPAI strains has been described for only the Asian HPAI virus H5N1. The ecologic and epidemiologic implications of this unprecedented situation are not predictable.

On the contrary, viruses that belong to all subtypes (H1–H16) that lack the multibasic cleavage site are perpetuated in nature in wild bird populations. Feral birds, particularly waterfowl, are the natural hosts for these viruses and are therefore considered an ever-present source of viruses. Since their introduction into domestic bird populations, these viruses have caused low-pathogenicity avian influenza (LPAI), a localized infection that results in mild disease, primarily respiratory disease, depression, and egg-production problems. Theories suggest that HPAI viruses emerge from H5 and H7 LPAI progenitors by mutation or recombination (2,3), although >1 mechanism is likely. This theory is supported by findings from phylogenetic studies of H7 subtype viruses, which indicate that HPAI viruses do not constitute a separate phylogenetic lineage or lineages but appear to arise from nonpathogenic strains (4,5); this indication is supported by the in vitro selection of mutants virulent for chickens from an avirulent H7 virus (6).

Such mutation probably occurs after the viruses have moved from their natural wild-bird host to poultry. However, the mutation to virulence is unpredictable and may occur very soon after the virus is introduced to poultry or after the LPAI virus has circulated in domestic birds for several months. This hypothesis is strongly supported by a recent study of Munster et al. (7), who showed that minor genetic and antigenic diversity exists between H5 and H7 LPAI viruses found in wild birds and those that caused HPAI outbreaks in domestic poultry in Europe. The scientific evidence collected in recent years leads to the conclusion that not only must HPAI viruses be controlled in domestic populations, but LPAI viruses of the H5 and H7 subtypes should also be controlled because they represent HPAI precursors.

Prevention of Avian Influenza

From December 1999 through April 2003, >50 million birds died or were depopulated after HPAI infection in the European Union (1), causing severe economic losses to the private and public sectors. These losses suggest that the strategies and control measures used to combat the disease need improvement, from disease control and animal welfare perspectives.

AI viruses are introduced to domestic poultry primarily through direct or indirect contact with infected birds. Transmission may occur through movement of infected poultry; movement of contaminated equipment, fomites, or vehicles; and exposure to contaminated infectious organic material. Airborne transmission over long distances between farms has not yet been demonstrated. For these reasons, if biosecurity measures are implemented at the farm level, AI infections can be prevented.

Outbreaks that involve large numbers of animals are characterized by the penetration of infection into the commercial circuit; that is, industrially reared poultry and all other poultry that is traded, including those from semi-intensive and backyard farms. Biosecurity (encompassing bioexclusion and biocontainment) represents the first and most important means of prevention. If biosecurity measures of a high standard are implemented and maintained, they create a firewall against infection penetration and perpetuation in the industrial circuit. However, breaches in biosecurity systems do occur. On one hand, the occurrence and extent of the breach should be evaluated and corrective measures should follow; on the other, they indicate the need to establish early warning systems and additional control tools for AI.

General Aspects of Vaccination

Until recently, AI infections caused by viruses of the H5 and H7 subtype occurred rarely, and vaccination was not considered because stamping out was the recommended control option. Primarily for this reason, vaccinology for AI has not grown at the same rate as for other infectious diseases of animals. Data are being generated from experimental and field research in AI vaccinology, but the rather complex task of vaccinating poultry in different farming and ecologic environments still has areas of uncertainty.

Guidelines on disease prevention and control have been issued as joint recommendations of the World Organization for Animal Health (OIE), the Food and Agriculture Organization (FAO), and the World Health Organization (8). These recommendations, however, need to be put into practice in a variety of different field situations; the applicability of 1 system rather than another in a given situation must be evaluated, weighing the benefits of a successful result against the drawbacks of failure.

Vaccination can be a powerful tool to support eradication programs if used in conjunction with other control methods. Vaccination has been shown to increase resistance to field challenge, reduce shedding levels in vaccinated birds, and reduce transmission (9,10). All these effects of vaccination contribute to controlling AI; however, experience has shown that, to be successful in controlling and ultimately in eradicating the infection, vaccination programs must be part of a wider control strategy that includes biosecurity and monitoring the evolution of infection.

To eradicate AI, the vaccination system must allow the detection of field exposure in a vaccinated flock, which can be achieved by using conventional inactivated vaccines and recombinant vector vaccines. Conventional inactivated vaccines that contain the same viral subtype as the field virus enable detection of field exposure when unvaccinated sentinels left in the flock are tested regularly. This system is applicable in the field but is rather impracticable, especially for the identification of sentinel birds in premises that contain floor-raised birds. A more encouraging system, based on the detection of anti-NS1 antibodies, has been recently developed and can be used with all inactivated vaccines, provided they have the same hemagglutinin subtype as the field virus (11). This system is based on the fact that the NS1 protein is synthesized only during active viral replication and, therefore, is rarely present in inactivated vaccines. Birds vaccinated with such vaccines will develop antibodies to NS1 only after field exposure. Full and field testing of this system under different circumstances are still in progress (12,13), and results should be available before this system is recommended.

To date, the only system that enables detection of field exposure in a vaccinated population and that has resulted in eradication is based on heterologous vaccination and known as "DIVA" (differentiating infected from vaccinated animals). This system was developed to support the eradication programs in the presence of several introductions of LPAI viruses of the H7 subtype (1,9). Briefly, a vaccine is used that contains a virus possessing the same hemagglutinin, but a different neuraminidase, as the field virus. This vaccination strategy enables detection of antibodies to the neuraminidase antigen of the field virus. For example, a vaccine containing an H7N3 virus can be used against a field virus of the H7N1 subtype. Antibodies to H7 are cross-protective, thus ensuring clinical protection, increased resistance to challenge, and reduction of shedding, while antibodies to the neuraminidase of the field virus (in this case N1) can be used as a natural marker of infection. Experimental data on the quantification of the vaccination effect on transmission within a flock indicate that the reproduction ratio can be reduced to <1>11). Such a reproduction ratio indicates minor rather than major spread of infection. In simple terms, such vaccination interventions will substantially reduce (although not prevent) secondary outbreaks, depending on the immune status of contact birds and flock.

Promising results have also been obtained with vaccines generated by reverse genetics (12). These vaccines are expected to perform like conventional inactivated vaccines; however, data are not yet available as to their efficacy under field conditions. Recombinant fowlpox vaccines that express the hemagglutinin protein of the field virus have also been reported to be efficacious for reducing shedding levels and providing clinical protection (14). They enable the detection of field exposure because vaccinated unexposed animals do not have antibodies to any of the other viral proteins. Any test developed to detect antibodies to the nucleoprotein, matrix, NS1, or neuraminidase of the field virus can be used to identify field-exposed birds in a vaccinated population. However, the performance of these vaccines in relation to the immune status of the host to the vector virus is unclear (15). Recent encouraging studies indicate that vaccination of day-old chicks with maternal antibodies against fowlpox has been successful. Data are lacking on the performances of such vaccines in a population that has been field exposed to fowlpox. Another aspect that must be carefully considered is the host. These vaccines are likely to induce protective immunity only in birds that are susceptible to infection with the vector virus.

Regardless of the vaccine and companion test used, mapping occurrence of infection within the vaccinated population is imperative, primarily to monitor the evolution of infection and to appropriately manage field-exposed flocks. Field exposure represents a means by which infectious virus may continue to circulate in the immune population; for this reason, vaccination can be considered as only part of a control strategy based on biosecurity, monitoring, approved marketing procedures, and stamping out. An inappropriately managed vaccination campaign will likely result in the virus becoming endemic.

Inadequate biosecurity or vaccination practices can lead to transmission between flocks and selection of variants that exhibit antigenic drift. Antigenic drift of H5N2 viruses belonging to the Mexico lineage, resulting in lower identity (less similarity) to the vaccine strain, has been described (16). Extensive use of vaccine in Mexico has resulted in the emergence of antigenic variants that escape the immune response induced by the vaccine. This occurrence is similar to antigenic drift that typically occurs in animals with a long lifespan (pigs and horses) that are routinely vaccinated and in human beings. Mexico has been vaccinating poultry since the HPAI outbreak in 1994 without applying the DIVA principle. Although no HPAI virus has been reported since the implementation of the vaccination campaign, LPAI viruses continue to circulate. Conversely, a similar approach in Pakistan after the HPAI H7N3 outbreaks in 1995 resulted in the isolation of HPAI H7N3 virus ≈10 years later, in 2004 (17).

The international scientific community is debating how vaccination of poultry would affect human health. On one hand, vaccinated birds shed less virus; on the other, they do not show any clinical signs of disease and could therefore act as silent carriers. Several factors contribute to the development of infection in humans: insufficient hygienic standards, the characteristics of the strain, and presence of viral dose sufficient to infect a human being. The possibility that vaccinated poultry may not shed enough virus to infect a human being is substantiated by recent field evidence. With reference to the H5N1 crisis, several countries are using vaccination to support control efforts. Vietnam implemented a nationwide vaccination campaign, which was completed in early 2006. The campaign's main achievement is that despite 61 cases of human infection between January and November 2005, no human cases of AI have been reported in Vietnam after December 2005 (18).

Emergency Vaccination

Recent outbreaks in developed countries, notwithstanding their efficient veterinary infrastructures and modern diagnostic systems, have resulted in the culling of millions of birds. Since the year 2000, AI epidemics in areas densely populated with poultry have resulted in 13 million dead birds in Italy in 1999–2000 (H7N1), 5 million dead birds in the United States in 2002 (H7N2), 30 million in the Netherlands in 2003, and 17 million in Canada in 2004. For each of these episodes, biosecurity measures implemented at the farm level were insufficient to prevent massive spread of AI.

Emergency vaccination for AI has become an acceptable tool, in conjunction with other measures, for combating the spread of AI. Using emergency vaccination to reduce the transmission rate could provide an alternative to preemptive culling to reduce the susceptibility of healthy flocks at risk. The effectiveness of such a program depends on variables such as the density of poultry flocks in the area, level of biosecurity and its integration into the industry, characteristics of the virus strain involved, and practical and logistical issues such as vaccine availability and adequate and speedy administration. For this reason, contingency plans that include decision-making patterns under different scenarios should be formulated.

Pivotal work on emergency vaccination has been done in Italy. Application of the DIVA strategy has resulted in the approval of the use of vaccination as an additional tool for the eradication of 2 epidemics of LPAI (H7N1 and H7N3) without massive preemptive killing of animals. Vaccination complemented restriction measures already in place and was integrated into an intensive monitoring program that identified viral circulation in the area (9) and culled infected birds. In 2000, heterologous vaccination against an H7 virus was used for the first time in the field as a natural marker vaccine. Subsequently, a DIVA strategy was used by Hong Kong Special Administrative Region, People's Republic of China, to prevent the introduction of H5N1 into its territories (19).

Although use of a DIVA system enabled international trade of poultry products to continue (9,20), vaccination for AI is a new concept, which several countries are reluctant to even consider. Government authorities ultimately decide whether vaccination should be used in a given country; their reluctance is probably driven by legislative and scientific uncertainties, coupled with doubts about how this practice will be used in the field and other considerations such as exit strategy. With reference to trade implications, a new chapter of the OIE Terrestrial Animal Health Code on AI (21) enables the continuation of trade in presence of vaccination if the exporting country is able to produce surveillance and other data that confirm that notifiable avian influenza is not present in the compartment from which the exports come. This chapter is the result of extensive work by OIE experts and the OIE Central Bureau on the issue of reducing the effect of animal diseases through the use of vaccination and is contained in a recommendation document issued as a result of an International Conference held in Buenos Aires (April 14–17, 2004) that strongly supports the use of vaccines for diseases on List A (22).

Prophylactic Vaccination

Prophylactic vaccination for viruses of the H5 and H7 subtypes is a completely innovative concept, primarily because only recently have cost-effective situations been identified. Prophylactic vaccination should generate a level of protective immunity in the target population; the immune response may be boosted if a field virus is introduced. Prophylactic vaccination should increase the resistance of birds and, in the case of virus introduction, reduce levels of viral shedding, provided the same levels of biosecurity are maintained. It should be perceived as a tool to maximize biosecurity measures when risk for exposure is high. Ideally, it should prevent the index case. Alternatively, it should reduce the number of secondary outbreaks, thus minimizing the negative effects on animal welfare and potential economic losses in areas where the density of the poultry population would otherwise result in uncontrollable spread without preemptive culling.

Prophylactic vaccination should be considered only when circumstantial evidence indicates that a given area is at risk. Risk for infection may be divided into 2 categories: 1) high risk for infection with either H5 or H7 subtype (e.g., from migratory birds), and 2) risk for infection with a known subtype (e.g., H7N2 in live bird markets in the United States, countries with high exposure to H5N1). For the first category, a bivalent (H5 and H7) vaccination program could be implemented. Italy has recently implemented such a program in the densely populated poultry area at risk for infection (23). For the second category, a monovalent (H5 or H7) program would be sufficient.

The choice of vaccine is crucial to the outcome of prophylactic vaccination campaigns. Ideally, vaccines that enable detection of field exposure with any AI virus should be used. Such candidates would be vaccines that enable the identification of field-exposed flocks through the detection of antibodies to an antigen that is common to all type A influenza viruses such as NP, M, or NS1. Such a strategy would detect the introduction of any subtype of AI.

The DIVA system, which uses heterologous neuraminidase, has some limitations in its application for prophylaxis or in situations with risk for introduction of multiple AI subtypes because the system was originally developed to fight a known subtype of AI. The main problem is that the virus against which vaccination is directed must have a different N subtype than the virus present in the vaccine, which, for prophylactic vaccination, is impossible to establish beforehand. An approach to resolving this difficulty is to use seed vaccine strains of the H5 and H7 subtypes that are exhibiting rare neuraminidase subtypes such as N5 or N8. This selection criterion of vaccine strains will greatly reduce the chance that an AI virus of a similar N subtype is introduced. In any case, for surveillance purposes, unvaccinated sentinels should be present in the flock.

Prophylactic vaccination should be continued as long as risk for infection exists. It can be used in a targeted manner for limited periods of time, which requires a detailed exit strategy.

Conclusions

The scientific veterinary community must control AI infections in poultry for several reasons: to manage the pandemic potential, to preserve profitability of the poultry industry, and to guarantee food security to developing countries. Although biosecurity is recognized as an excellent means of preventing infection, in certain situations the biosecurity standards necessary to prevent infection are difficult to sustain. Vaccination is a potentially powerful tool for supporting eradication programs by increasing the resistance of birds to field challenge and by reducing the amount and duration of virus shed in the environment. Vaccination strategies that encompass monitoring of infection in the field are crucial to the success of such efforts.

Timely information is needed about the efficacy of vaccination in a variety of different avian species, bearing in mind the diverse farming systems used in developed and developing countries. The outcome of such efforts should be made available to the international community because decision makers lack enough information to make educated choices. An enormous effort is required from national governments and funding bodies to make resources available to research programs to develop improved control measures that can be applied under different local conditions. To maximize the global effort to combat this disease, developing and sustaining transversal research programs on AI control, which encompass veterinary and agricultural science, are imperative.

Dr Capua, a veterinary virologist, is head of the OIE/FAO Reference Laboratory for Avian Influenza and Newcastle Disease and head of virology at the Istituto Zooprofilattico Sperimentale delle Venezie.

Dr Marangon, a veterinary epidemiologist, is director of science, Istituto Zooprofilattico Sperimentale delle Venezie.

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Suggested Citation for this Article

Capua I, Marangon S. Control of avian influenza in poultry. Emerg Infect Dis [serial on the Internet]. 2006 Sep [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no09/06-0430.htm

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Ilaria Capua, OIE and National Reference Laboratory for Newcastle Disease and Avian Influenza Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell'Università 10 35020 – Legnaro, Padova, Italy; email: icapua@izsvenezie.it

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