VOL 10 | MAY 2016 Rational use of Contributors: Les Simsa, Astrid Tripodib, Sophie von Dobschuetzb, for prevention and control of Emma Gardnerb, Ryan Aguannob

a, b H5 highly pathogenic avian (See back cover) influenza

Abstract/overview to achieve high-level immunity in vaccinated populations through use of appropriate, lo- accination can play a valuable role in con- cally-registered and implementation Vtrol, prevention and elimination of highly of post-vaccination monitoring; iii) passive 1 pathogenic (HPAI) viruses. In surveillance systems able to identify flocks in Abstract/overview places where HPAI remains endemic, which virus might be circulating so that these 1 has been used to reduce the quantities of vi- can be reported and investigated; iv) applica- Why opt for vaccination? rus shed into the environment, which, in turn, tion of other appropriate management prac- reduces human exposure and the likelihood of tices and biosecurity measures at farms and 3 zoonotic and pandemic influenza, as well as markets aimed at reducing the risk of Principles of rational vaccine use the risk of severe disease in poultry. In other with HPAI: and v) an appropriate cost-sharing 4 countries (China, Hong Kong SAR and Mexico), mechanism with the private sector. ˜ Key questions in designing a vaccination has been used successfully to as- vaccination strategy for sist in the elimination of virus. Despite these Why opt for vaccination? disease prevention and control positive experiences, considerable resistance to use of vaccine exists because of perceived ince it emerged in 1996, HPAI caused by 6 and actual adverse consequences associated Goose/Guangdong-lineage H5 viruses (H5 Potential drawbacks of vaccine use S with vaccination as well as concerns about HPAI) has become a major risk and constraint 7 availability of sufficient resources to conduct to poultry production on four continents and Does use of vaccination lead vaccination programmes. The adverse effects a cause of sporadic severe zoonotic disease to endemic infection? can be overcome or managed, and benefits of in humans. It also remains as a potential hu- vaccination maximized if vaccine is used ra- man pandemic influenza threat. In most plac- 7 tionally. Rational use involves five core prin- es, control of avian influenza can be achieved Conclusion ciples and requires: i) clear objectives and primarily by stamping out. However, the ef- 8 regular reviews of progress towards these fectiveness of this strategy depends on early References objectives; ii) design of the programme so as detection of all infected poultry and swift ac-

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Table 1

Different scenarios for the use of vaccination as a tool in HPAI control

Scenarios Recent outbreak in When stamping out With no prospect of a country previously alone is not achieving virus elimination in free of the virus virus elimination in an the next 2+ years in an infected country endemic country Objective Virus elimination Virus elimination Outbreak containment and reduction in virus circulation Use of vaccination and Emergency Targeted vaccination Targeted vaccination; ©FAO/Sia Kambou ©FAO/Sia other measures vaccination with added as a control Less emphasis on An aviary technician vaccinates a chicken at a stamping out measure to facilitate stamping out; training session for poultry farmers in Chad. stamping out Introduce changes to farm and market practices to reduce risk Vaccines Need to have a Locate and use Locate and use stockpile of suitable suitable vaccine suitable vaccine vaccine Other requirements Rapidly detect all Detect infected flocks Regularly review infected flocks and and take swift action; scope, effectiveness take swift action and the need for Regularly review vaccination. scope, effectiveness and the need for If/when feasible revert vaccination to virus elimination

Duration Short (if successful) Short to medium Usually long Tripodi ©FAO/Astrid Vaccination is performed on newly hatched Note: Distinct from Nepal isolates; detected in poultry and wild birds (crows). chicks.

tion to prevent these birds from spreading the ing shedding of the virus in those birds that Minimizing unwanted consequences: When virus. The costs of stamping out are high, not do become infected. Unvaccinated infected implementing a vaccination programme, sev- only in terms of the intervention itself but be- chickens shed much higher concentrations eral challenges need to be faced, all of which cause of the compensation provided to affect- of virus than their vaccinated, infected coun- can be overcome or minimized. Concerns in- ed owners, which is necessary to encourage terparts (Swayne, 2006). Once vaccinated, clude: reporting and to help defray losses to people’s marked reduction of onward transmission of ƒƒ viral shedding in clinically healthy, vacci- livelihoods. virus can occur within seven days post-vac- nated birds, or the so-called “silent infec- Evidence suggests that virus elimination in cination (van der Goot et al., 2005). In one ex- tion” (see, for example, Poetri et al., 2014); poultry is unlikely in a number of countries ample in China, Hong Kong SAR, in which vac- ƒƒ the use of vaccination as a substitute for where the virus remains endemic (FAO, 2012). cination was used in the face of an outbreak, other important measures, such as im- In these places, all available tools for preven- transmission ceased within 18 days (Ellis et provements to biosecurity; tion and control of the disease should be con- al., 2006). ƒƒ a false sense of security leading to the un- sidered, including vaccination using appropri- Despite the potential benefits of vaccina- derestimation of clinical signs consistent ate and quality biologicals. Table 1 provides tion, many countries continue to restrict their with HPAI or of milder clinical signs, jeop- possible scenarios for the use of vaccination. control options to stamping out even after it is ardizing the immediate detection of HPAI in Control and elimination of H5N1 is achieved evident that this method is not working as in- vaccinated flocks (Vergne et al., 2012); by reducing the number of infected and sus- tended. This creates a major burden for poul- ƒƒ the potential impact on trade in poultry ceptible poultry, thereby also reducing the try producers and does not halt the spread products (Pongcharoensuk et al., 2012; amount of circulating virus able to establish of disease as farmers will often sell flocks ƒƒ the emergence of antigenically variant onward transmission. of poultry when they first notice increases in strains (Cattoli et al., 2011). Vaccination can help achieve these objec- mortality, which, in turn, exacerbates the out- Though each of these concerns is legit- tives by increasing resistance to infection, de- break and increases the public health risk in imate, the rational use of vaccination can creasing the likelihood of disease and reduc- the case of zoonotic influenza viruses. help ensure that the overall effect remains

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Box 1 Box 2

Real-life examples: Success of vaccination against avian influenza – Real-life example: Selling of sick birds China, Hong Kong SAR, Italy, Mexico, United States of America, Viet Nam – a report from the 2006–2008 Nigerian outbreak

Vaccines were first used successfully against low pathogenic avian influenza (LPAI) viruses and these experiences demonstrated the potential for use against highly pathogenic avian influenza In an assessment of market chains in (HPAI) viruses. Poultry in turkey farms in the United States of America were among the first Nigeria conducted in 2008, it was found to be vaccinated successfully against a range of LPAI viruses (Halvorson, 2009). Vaccination that when birds get sick, 41 percent of since has been used effectively in a number of places including northern Italy (LPAI), Mexico respondents organize salvage slaughter, 31 (H5 and H7 HPAI) and China, Hong Kong SAR (H5 HPAI) to prevent infection and to control and percent isolate the sick birds for treatment eliminate virus. In these places, vaccination was coupled with other measures such as raised and 27 percent sell the sick birds at low biosecurity standards, active surveillance and stamping out. Other countries where avian prices (FAO, 2008). This demonstrated that influenza virus was endemic and where stamping out had not achieved the desired goal have disease reporting was not occurring, which used vaccination to reduce viral loads. The experiences with HPAI in Viet Nam during 2003–2004 can reduce the effectiveness of stamping warrant consideration given that some 45 million head of poultry had been lost, most through out. This assessment was done shortly culling. This loss represented 17 percent of the total standing poultry population. It is likely that after payment of compensation had been depopulation did reduce viral loads, but by 2005, Viet Nam was experiencing more human cases discontinued. of Influenza A(H5N1) disease than any other country, demonstrating that any positive effects from the stamping out were short-lived. Poultry vaccination, along with a number of other measures, was implemented to reduce human health risk resulting in a marked reduction in human cases. Viet Nam continues to use vaccination and conducts regular review of the need posed to the virus), delivery of killed antigen for vaccination, the scope of the programme and the vaccines to be used. vaccine in the progeny should be delayed for approximately one week (to three weeks of age). The efficacy of killed antigen vaccines is determined by the antigenic relationship positive. To overcome these concerns, vac- What vaccines are available? between the vaccine and field strain, the im- cination programmes should be designed to munogenicity of the antigen and the quantity maximize benefits and minimize unwanted Two main types of poultry vaccine are availa- of antigen in each dose. Effectiveness in the consequences. ble for avian influenza at present: killed anti- field is influenced by: the manner of vaccine Appropriate timing: The option to vaccinate gen in an oil-based adjuvant and vaccines that storage prior to administration (the vaccines should be assessed early in the face of dis- rely on a viral vector to deliver the antigen. require maintenance at 4–8°C as they are not ease and should not be considered as a last Killed antigen vaccines have been used for heat-stable); concurrent immunosuppressive resort. Regular review points that consider decades in the prevention and control of avian diseases in vaccinated birds; and species of the possibility of vaccination should be in- influenza and work effectively. They require in- bird and the , including cluded in HPAI contingency plans. Apart from dividual injection of birds and usually multiple age of first administration. the benefit of controlling disease, the use of doses are needed starting at about two weeks As these vaccines contain whole (inactivat- vaccination can help to: of age. In some countries, a withdrawal peri- ed) virus, antibody is generated to the hae- ƒƒ reduce the cost of control when effective od applies before birds can be sent to slaugh- magglutinin (HA) and neuraminidase (NA) vaccine delivery can be ensured; ter for consumption, as specified by the man- proteins of the antigen. The antibody to the ƒƒ decrease disruptions to the poultry sector; ufacturer and/or veterinary authorities. This HA is most important for protection from dis- ƒƒ secure public health; can limit the value of vaccination in short- ease and for reducing viral shedding. ƒƒ protect high value stock – Note: in those lived meat birds. (However, no known public A number of different viral vectors have endemic countries where vaccination is health risk is associated with consumption of been used for delivering HA antigens includ- prohibited, smuggling and use of vaccine of a vaccinated chicken; the withdrawal period is ing fowl pox virus, Newcastle disease virus, unknown origin and potency by the private related to the additives mixed in the vaccine to alphavirus replicons and herpes virus of tur- sector is to be expected and has occurred improve its stimulatory properties or preserv- keys. Several experimental vectors are also (Sims, 2013); atives). Maternal antibodies (conferred via being assessed including duck enteritis virus. ƒƒ control the virus when it has become en- egg yolk in the embryo) can interfere with the Some of these vaccines appear to be effec- demic despite implementation of other immune response generated by these vac- tive in the presence of maternal antibodies measures; cines (Maas et al., 2011) and generally vanish and can be administered in ovo or at hatch- ƒƒ maintain consumer confidence and miti- by two to three weeks of age after hatching. ing (Rauw et al., 2012). Vectored vaccines may gate potential market shocks. When these are expected to be present (if afford broader protection against viruses of parent stock has been well vaccinated or ex- different strains and clades, perhaps, in part,

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because they also stimulate cell-mediated necessary. The objectives must justify the ac- al., 2015). Regulation of licensed vaccines is immune responses. Nevertheless, it is pref- tivities carried out. For example, large-scale necessary to avoid the use of inefficient/inef- erable for the HA insert in the vector to be a vaccination of smallholder and household fective vaccines. A properly managed govern- reasonable match to the circulating strains poultry flocks, with birds of different ages ment vaccine registration/licensing process of virus. Most vectored vaccines are used to and rapid turnover, can usually only be justi- is, therefore, needed. It may be necessary to prime the immune system and are followed fied on public health grounds and then only if de-register vaccines if significant antigen- several weeks later by a dose of killed vac- resources are available to ensure that appro- ic drift3 occurs or new strains of virus are cine. Vaccine research development is ongo- priate levels of flock immunity are maintained detected through monitoring programmes ing and constantly evolving (see, for example, in these birds (especially during periods of against which existing vaccines provide little Kapczynski et al., 2016, Rahn et al., 2015). high risk of transmission). Past experience or no protection. Governments can enter into Apart from efficacy in the target popula- suggests that this is difficult to maintain over contracts with private/academic institutions tion, the choice of vaccine will depend on large areas but can be successful at the local to carry out this function. A coding system for other factors, including price and availability. level. the different vaccines to be tested should be These factors can change over time, providing The programme should include clear goals used to rule out subjectivity (such as manu- additional reasons for regular review of vac- and criteria for ending vaccination.1 Vaccina- facturer preference). Facilities producing vac- cination strategies and management of the tion should be used for as long as is neces- cines should be separate from agencies that programme. ˜ sary to control and prevent infection and may verify the vaccine's quality and efficiency. be required for an extended period in places Principles of rational where the virus is entrenched and prospects Agreements should be in place to ensure vaccine use of virus elimination are poor. Vaccination can 3that farmers immediately alert veteri- be stopped when the disease is controlled nary authorities in case of mortality of vac- or eliminated, when the risk of re-incursion cinated poultry above agreed baseline levels. Five core principles of is low, and when new outbreaks can be de- This will facilitate early detection of vaccine rational vaccine use tected and managed rapidly. It is possible to failures or antigenic variant viruses that may use emergency vaccination even after routine arise during the course of a vaccination pro- use of vaccination ceases. Unrealistic time gramme. If increased mortality due to avian 1. Set clear objectives and regularly review lines on the expected duration of vaccination influenza occurs in a vaccinated flock, the strategies for vaccination, consistent programmes should be avoided especially in government should provide appropriate and with the overall prevention and control places where infection is already widespread. timely compensation4 for the flock owner if plan. the flock is destroyed. 2. Use high-quality vaccines, registered by Only high quality vaccines that are a good national authorities, shown to be a good antigenic match to circulating strains and Wherever possible, vaccination should be antigenic match to the circulating field 2 at an appropriate dose should be used. They accompanied by other measures to re- strain(s). 4 should be produced in accordance with good duce the likelihood of exposure to and trans- 3. Strengthen the passive surveillance management practices using international mission of the virus. These should include system and farmer compensation standards.2 They should also be good immu- enhanced farm and market biosecurity scheme especially if virus elimination nogens, i.e. able to induce a good immune re- measures such as all-in-all-out flock man- remains the immediate goal. sponse in vaccinated birds. agement, banning overnight stay of birds in 4. Strengthen concurrent biosecurity Before implementing a large-scale vacci- markets, etc. (FAO, 2015a; FAO, 2015b; FAO, measures and good farm management nation programme the effectiveness of the 2015c). For some production systems, such practices. vaccine(s) chosen should be assessed un- as free-grazing ducks, the only biosecurity 5. Agree on a cost-sharing scheme der laboratory and field conditions against measures available are reducing direct and between public and private sectors, circulating viruses. The levels of antibody in indirect contact between domestic ducks and based on vaccination objectives. vaccinated chickens to field virus generally other types of poultry, and tight movement correlate with levels of protection; (high an- management. The potential for spread of vi- The vaccination programme must have tibody titres against the field strain provide rus by vaccinators moving between premises 1clear objectives, established by govern- better protection than low titres and can pre- must be recognized and appropriate hygiene ment in consultation with the private sector, vent virus shedding and disease) (Swayne, et measures put in place, including cleaning and that relate to the overall prevention and con- trol plan (such as mitigating production loss- 3 Antigenic drift: small changes in the genome of 1 es and reducing human exposure to virus). It This is often termed ‘exit strategy’. influenza viruses that happen continually over time 2 For procedures see the OIE Manual of Diagnostic during virus replication, eventually changing the anti- must be assessed regularly (at least annually) Tests and Vaccines for Terrestrial Animals, at http:// genic properties of the virus. in order to review progress towards the objec- www.oie.int/fileadmin/Home/eng/Health_standards/ 4 For more information on compensation please see tives and update or modify the objectives as tahm/2.03.04_AI.pdf. http://www.fao.org/avianflu/en/compensation.html

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tivalent vaccines containing different antigens can be used provided appropriate quantities of each antigen are incorporated (that is, at levels equivalent to monovalent vaccines for each antigen). Ultimately, the best test for a killed anti- gen vaccine is a laboratory challenge study under a high biosafety and biosecurity en- vironment using birds vaccinated at three weeks of age and challenged three weeks later. Challenge studies with the circulating field strain(s) should be conducted in places where appropriate facilities are available. It

©FAO/C.Y. Gopinath ©FAO/C.Y. may be possible to obtain relevant informa- Poultry vaccination against H5 avian influenza, along with a number of other measures, was tion from other countries that have tested implemented in Viet Nam in 2003–2004 to reduce human health risk. vaccines against similar viruses. If a suitable vaccine is not available it may be necessary to have one manufactured from a local strain disinfection of boots or change of boot covers ten poor in areas with a high density of poul- of virus (or closely related strain) in facilities and coveralls between farms, and disinfection try farms. This is the situation in the places using good management practices. In most or change of vaccination equipment. where H5N1 HPAI viruses remain endemic cases, it is better to have this done by com- (FAO, 2011). panies that specialize in this area; (if several Cost-sharing of vaccination (and post-vac- Guidance for the decision-making pro- vaccines are to be tested, a system of ‘coding’ 5cination monitoring) should be applied be- cess has been developed (Castellan et al., is urged). Use of an unmodified HPAI virus as tween the government and the private sector. 2014, OFFLU, 2014). Key questions for deci- a seed strain is not generally recommended If industry will derive significant production sion-making on vaccination are: due to the potential risks from insufficient and marketing advantages from vaccination, antigen production or, if zoonotic, to possible they should pay most of the costs. A case for Is a suitable vaccine available? Could one be occupational hazards. Most vaccine antigens subsidized vaccination can be made if the made available? And how is it to be admin- are natural LPAI strains or are HPAI strains main purpose is to protect public health. ˜ istered? genetically modified to become LPAI viruses. Decision-making requires assessment of the The OIE/FAO Network of Expertise on Animal Key questions in designing a antigenic characteristics of existing viruses Influenzas (OFFLU) can advise on this pro- 5 vaccination strategy for disease in the field and comparison with available cess. prevention and control vaccines and vaccine antigens. It also re- quires ongoing monitoring for changes from Is a vaccine antigen which is a good antigenic In deciding whether or not to use vaccination, antigenic drift in existing viruses or the in- match also a good immunogen? the key question to ask is: troduction of a new strain (e.g. in Indonesia Not necessarily. Not all virus strains are equal where introduction of a well-matched vaccine as immunogens as some appear to stimulate Can vaccination assist in prevention and con- was followed by improved control of clade 2.1 a stronger level of immunity than others. This trol of avian influenza and reduce the risk of viruses and the introduction of clade 2.3.2.1 may be due, in part, to the glycosylation pat- human cases and, if so, how? H5N1 virus in 2012 was followed by introduc- terns of the HA protein. Immunogenic perfor- In answering this question, the effectiveness tion of vaccination against this strain). mance of vaccine antigens is best evaluated of existing control and preventive measures It is preferable to assess vaccines against a in challenge experiments (Zhang et al., 2015). must be assessed, as well as their costs (eco- number of local viruses as there can be sub- nomic and social) compared to those of vacci- tle differences. This assessment is important What types of poultry should be prioritized nation. Synergy between methods may mean in places where the virus has been present for vaccination? that some costs associated with stamping out for some time and has evolved into differ- This is a crucial question. can be reduced if vaccination is used. ent sublineages (Spackman et al., 2014). It If the main target population is chicken lay- Another important issue that needs to be is also necessary to perform in vitro testing ers or parent flocks then it is possible to de- considered is the efficiency of case detec- (i.e. cross HI tests using sera from vaccinated velop high-level immunity in these birds prior tion. If a high proportion of cases are unde- poultry versus the vaccine antigen and field to the point of lay (usually using a three-dose tected and action is not taken early enough to antigens), which can also be used for antigen course of vaccine). prevent virus transmission, the likelihood of mapping, an aid in antigen selection for inclu- disease elimination using stamping out is of- sion in the vaccine (Swayne et al., 2015). Mul- 5 Please contact [email protected]

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How can existing vaccination programmes be leveraged for vaccination against AI? Most industrially-reared poultry are being vaccinated against other diseases such as Newcastle disease, infectious bursal disease or duck viral enteritis. In these situations, if appropriate systems are in place to ensure these products are delivered to birds and the vaccines are correctly stored along the entire chain, then similar systems can be implement- ed for AI vaccines. Another issue to consider for large poultry flocks is that killed antigen vaccines require injection of individual birds.

Can high-level immunity be generated in the target population? One objective of all vaccination programmes is to achieve high-level immunity in vacci- nated flocks. It is usually possible to do so in

©FAO/E. Amalore ©FAO/E. relatively long-lived poultry, especially when A hatchery employee examines recently hatched ducklings. birds are reared on an “all-in/all-out” basis. Layers may not generate sufficient levels of immunity during the end stages of their life, vaccination at around two weeks of age and which can be further complicated by the hes- boost after four weeks. Examples include itance of farmers to vaccinate birds in lay Chinese-style yellow-feathered birds that are due to perceived egg production losses. Poor usually reared for at least 70 days before en- nutrition or the presence of other infectious tering the consumer market. agents on a farm may influence the immune Vaccination of birds reared by small-scale response generated by vaccines (e.g. concur- producers is not normally recommended rent infection with infectious bursal disease since maintaining adequate levels of im- virus can compromise the immune response munity and instituting significant changes to avian influenza vaccination). Post-vacci- 6 ©FAO/Isaac Kasamani ©FAO/Isaac in hygiene practices proves very difficult in nation monitoring (PVM) of antibody levels Rwanda - A poultry farmer feeding the settings with a high turnover of poultry given in selected vaccinated flocks should be used chickens on his farm. the associated costs of the programme. The to assess the response to vaccination and to exception is in areas where large numbers make changes to the vaccination programme of human cases are occurring. However, the based on field investigations if levels of immu- Meat birds that live for less than 50 days are logistical difficulties of implementing large- nity are lower than expected or required. The not good candidates for use of killed antigen scale vaccination across thousands of house- number and type of flocks and the number of vaccines, as it is not usually possible to obtain hold flocks must be recognized. birds per flock to test will vary from place to high-level immunity with only a single dose In some countries, there are large popula- place and need to be designed for each pro- of the currently available commercial killed tions of ducks. Effective vaccines and vaccina- gramme by an experienced epidemiologist. vaccines. However, it may be possible to use tion schemes for ducks have been more diffi- The monitoring programme represents only a hatchery vaccination (i.e. vaccination of day- cult to achieve than for chickens. Vaccination small part of the overall cost of a vaccination old chicks) with an appropriate vector vaccine of ducks can reduce viral shedding if there campaign. followed by one or more booster doses of is a very good antigenic match between the As a rule, a single dose of a killed antigen killed antigen vaccine, with the first booster vaccine strain and the field strain, and suffi- vaccine is not sufficient to produce a strong usually given two to three weeks later. If a cient doses of vaccine are administered. Sin- and long-lasting immunity and should only be vectored vaccine is used on day–old chicks, it gle dose vaccination does not usually provide used for emergency vaccination. must be able to work in the presence of ma- appropriate protection from viral shedding. 6 ternally derived antibodies to the vector and Limited information is available on the effects Cut-off titres need to be established. As a general rule a titre of 1:32 in chickens against the field strain the avian influenza virus. of vaccines in other poultry species, although will prevent mortality and a titre of 1:128 will normally When meat chickens are kept for more than some studies have been performed on zoo- prevent shedding of virus if the birds are subsequently 50 days it is possible to obtain protection by logical collections (Koch et al., 2009). exposed to the virus (Swayne et al., 2015).

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Issues arise with household-level flocks logical tests that distinguish antibodies gen- nication strategies should promote passive where there is a high turnover of poultry, erated via infection in vaccinated birds (DIVA surveillance. In parallel with vaccination, bi- which results in a rapid reduction of flock im- strategy; i.e. detecting infection in vaccinated osecurity improvement programmes such as munity. This challenge can be overcome with animals). The former provides more imme- FAO models in Viet Nam and Indonesia (FAO, strong local coordination and responsive vet- diate information on the infection status of a 2015a; FAO 2015b) can and should be imple- erinary services so that new poultry are vac- flock when managed appropriately. Suitable mented. Farmer notification of infected vacci- cinated as they reach the appropriate age, as criteria need to be set for alerting veterinary nated flocks can be encouraged by ensuring specified in the manufacturer’s guidance, and services (e.g. doubling of daily mortality or appropriate compensation is available if a re- as previously discussed. a >30 percent fall in egg production). These port of disease results in the destruction of a trigger-points are only of use in places where flock, and by setting lower trigger-points that What percentage of poultry needs to be vac- farmers keep flock records – a good practice generate an investigation. This requires good cinated or immune? which is highly recommended. cooperation between industry and govern- Much of the research in this area is theoret- If widespread silent infection is occurring, ment veterinary services. ical and has assumed that the objective of the vaccine antigen should be examined to It is highly encouraged to have the veter- vaccination is virus elimination. In practice, assess whether it is still working against cir- inary public sector meet with industry and percentage of poultry to be vaccinated de- culating strains of virus and, if not, a new an- other poultry producers on a regular basis. pends on a number of factors including the tigen should be developed and used. Similarly, the veterinary public sector should current objectives of the control programme, engage the private professionals to share in- the stage of the vaccination programme and Concerns regarding vaccination formation and provide guidance. the types of housing and poultry. leading to a false sense of security Vaccine use should induce a sufficiently Concerns about impact on trade high level of immunity in the majority of the A reduction in farmer notification of out- vaccinated poultry. In general, vaccination breaks to veterinary services following intro- The effect of vaccination on trade is a genuine should aim to have 70 to 80 percent of birds duction of vaccination, as was occurring in concern that needs to be addressed between with acceptable, protective antibody titres. Egypt (Vergne et al., 2012), indicates the im- trading partners, preferably during periods In most cases this will require a minimum of portance of avoiding a false sense of security when the disease is not occurring. It has been two doses of vaccine (and additional doses in amongst vaccinated farms. It is important for one of the main factors inhibiting uptake of long-lived poultry). ˜ all involved to recognize that vaccination is vaccination, even in emergency situations, not a ‘magical solution’ and will not solve all (e.g. Thailand and the United States of Ameri- Potential drawbacks of problems. Expectations need to be tempered. ca), but one that can be overcome with appro- vaccine use Appropriate risk communication strategies priate surveillance and monitoring systems which highlight that vaccination alone will not in place. In countries with minimal export Concerns about silent infection prevent all signs of avian influenza infection trade (e.g. Indonesia, Viet Nam) the concern can help ensure biosecurity measures are remains limited. When a vaccinated bird is exposed to a HPAI continued. At the same time, these commu- virus there are three potential results: i) no clinical disease and little to zero quantities of virus are shed; ii) sufficient antibodies to prevent clinical disease but some viral shedding; and iii) full clinical disease (Ku- mar et al., 2007). When a flock is vaccinated, a range of antibody titres will be developed. If a HPAI virus enters a vaccinated chicken flock, those birds with low or no antibody ti- tres will die if infected, indicating infection in the entire flock. With only a few deaths in this case, infection is more subtle to detect than in non-immune flocks where mortality will be much higher. Many of the so-called silent actually occur as unreported mor- talities in these situations. The virus can be detected in infected flocks

through dead bird testing on vaccinated farms Filippov ©FAO/Alexey or, alternatively, through discriminatory sero- A backyard chicken flock belonging to a household in the Ukraine.

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Concerns about the development of antigenic variant strains of virus

The possibility that antigenic variants could emerge in places where vaccine is being used has been recognized since vaccination was first introduced for Goose/Guangdong-line- age (Gs/GD-lineage) H5N1 HPAI. Circulation of antigenically variant strains may result in insufficient protection of vaccinated flocks and can lead to outbreaks in vaccinated popu- lations. Monitoring of circulating field viruses and vaccine matching is therefore critical. With the exception of China and Indone-

sia, which have systems in place for regular Palma ©FAO/Saul updating of vaccine antigens, most develop- A chicken and chicks perching on a rock in Nicaragua. ing countries that vaccinate are still building systems for vaccine updates. Progress has year) so that they can prepare human vaccine ƒƒ Vaccinated flocks are not sufficiently mon- been made in identifying antigenic variant antigens for pandemic preparedness (WHO, itored. viruses in most countries, but the next step 2015). This valuable information can only be ƒƒ Farmers do not see any need to report in- of updating vaccine antigens is less well ad- obtained if there are appropriate monitoring creased mortality in vaccinated flocks. vanced. Both China and Indonesia often have systems in place to detect virus in poultry in ƒƒ Farmers vaccinate poultry at inappropriate a 12 to 24-month period between emergence places where vaccine is used. ˜ ages. of a new strain and production/uptake of a ƒƒ Farmers mix vaccinated with unvaccinated vaccine incorporating the new antigen (as Does use of vaccination lead to poultry. was the case with clade 2.3.4.4 viruses that endemic infection? ƒƒ Farmers see vaccination as the answer to emerged as an important cause of losses to all their problems. poultry producers in China from 2013). erhaps the main concern raised by coun- ƒƒ Vaccination assists in driving antigenic Genetic changes can potentially enhance Ptries and their agriculture or public change, thereby reducing the value of ex- human infectivity or virulence and novel anti- health authorities is that use of vaccination isting vaccines (unless vaccine antigens are genic variant strains need to be identified for may allow viruses to remain endemic or fa- regularly updated as needed). pandemic preparedness. Therefore, informa- cilitate development of endemic infection ƒƒ These issues need to be considered and ad- tion on genetic and antigenic characteristics because immunity is not sterilizing.7 Despite dressed in the design stage of a vaccination needs to be shared by national governments being a legitimate concern, it is also impor- strategy. ˜ with the World Health Organization (WHO) in a tant to recognize that in certain places where timely and regular manner (i.e. at least twice a vaccination is being applied, the virus would Conclusion remain endemic even if vaccination was not being used (as was or is the case in China, f used rationally, vaccination can help to Egypt, Indonesia and Viet Nam). Vaccination Icontrol and even eliminate HPAI. Vaccina- in these places was introduced as a response tion is not a ‘magic solution’ that will solve all to endemic or widespread infection. problems and should be used in conjunction Vaccination can contribute to an endemic with other control and preventive measures. situation if the following occur: Unless managed appropriately, it can cause ƒƒ Vaccination is not markedly reducing the some unintended consequences. Vaccina- levels of shedding of virus in vaccinated tion should be considered by all countries birds that are exposed to virus (owing to, struggling to control HPAI using stamping for example, insufficient vaccine coverage out alone because it can help to contain the in the target population or area, poor anti- disease and reduce risk of human infection. genic match, poor quality vaccine or insuf- This document provides an outline of the ficient doses of vaccine). main issues that need to be considered when contemplating use of vaccination. Additional advice can be obtained directly from FAO or 7 This means that some vaccinated birds that are

©FAO/Seyllou Diallo ©FAO/Seyllou subsequently exposed to the virus will still become OFFLU. ˜ A young chick in a chicken coop - the Gambia. infected and shed virus.

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11 CONTACT

The Emergency Prevention System (EMPRES) is an FAO programme, founded in 1994, with the goal of Recommended citation enhancing world food security, fighting transboundary animal and plant pests and diseases and reducing Sims, L., Tripodi, A., von Doschuetz, S., the adverse impact of food safety threats. EMPRES-Animal Health is the component dealing with the Garnder, E. and Aguanno, R. 2016. Rational prevention and control of transboundary animal diseases (TADs). use of vaccination for prevention and control of H5 highly pathogenic avian influenza. FOCUS To subscribe or to ask for information about EMPRES-Animal Health send an e-mail to ON, No. 10, May 2016. Rome [email protected] or a fax to (+39) 06 57053023.

For more information visit us at http://www.fao.org/ag/empres.html Photo cover: ©FAO/Ami Vitale Photos back cover: ©Sleiman Mouawad EMPRES-Animal Health can assist countries in the shipment of samples for TAD diagnostic testing at a FAO reference laboratory and reference centre. Please contact [email protected] for information prior to sampling or shipment. Please note that sending samples out of a country requires an export permit from the Chief Veterinarian’s Office of the country and an import permit from the receiving country.

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