Presented at the International Symposium "The Challenge and Implication on Avian Influenza on Human Security: Sharing Problem, Sharing Solution". Session 1: Controversies in Vaccination on Poultry and Human to Prevent the Spread of Avian Influenza. Proceedings. July 13-14, 2006. Puri Agung, Sahid Jaya Hotel, Jakarta, Indonesia.
Tri Satya Putri NaiposposIntroduction
Avian Influenza (AI) is a disease of poultry characterized by lethargy and respiratory signs caused by type A influenza virus infections. Most of AI viruses are low pathogenic which associated with mild or severe clinical signs, egg production loss, mortality and financial loss, depending on the virus, the host, secondary infections and environmental factors. All Highly pathogenic avian influenza (HPAI) cases is caused by H5 or H7 subtypes and usually associated with high morbidity and mortality in commercial flocks (Halvorson 2004).
The number of outbreaks of HPAI in the last few years has been unprecedented: Hong Kong (1997, 2001-2003), Italy (1999), Chile (2002), the Netherlands (2003), Canada (2004), and the continuing outbreaks in East and Southeast Asia (2003-2005). In early 2006, recent AI outbreaks occurred in Europe, the Middle East and Africa have caused dramatic swings in poultry consumption, increased trade bans and sharp price declines.
Aside from causing great economic losses to poultry industry, it is becoming increasingly clear that certain HPAI viruses have the potential to directly cross the human-bird species barrier and may become a pandemic threat. To reduce the primary risk of human HPAI infection, it is crucial to prevent infection of poultry (van der Goot, et al 2005, FAO 2004).
The economical impact of HPAI is huge and has been distributed within the entire poultry market chain, affecting producers, consumers, and employees in the retail industry since it begun in July 2003 in Indonesia. Center for Agriculture Socio Economic Research and Development (CASERD) estimated that the value of birds lost between US$ 16.2 to 32.4 million (McLeod et al 2005). Currently, 27 out of 33 provinces were affected with around 20 million poultry dead or culled in control efforts, excluding those lost from backyard farms for which no accurate estimates are available.
The Government of Indonesia has taken a step to implement vaccination approach as one strategy in combination with other eight strategies, well-known as nine strategies, since the official announcement of the HPAI outbreak occurrence in January 2004. This approach was taken bearing in mind that where in such situations it is not feasible or desirable to do massive culling, biosecurity of farm/village/backyard cannot be improved, and there is significant challenge of higher risk of spread from intensive poultry trade movement within the country. Although OIE did not recommend the vaccination approach at the early outbreaks but, nowadays every country have their own policies to choose approach depend on the situation.
The purpose of this paper is to discuss the controversy as to whether vaccination for HPAI assists complicates or interferes with eradication program. This paper present an overview of the role of vaccination in HPAI control as well as the advantages and disadvantages of using conventional inactivated vaccines.
Vaccination of poultry is not a stand alone strategy
While biosecurity is the first line of defence against all AI viruses, vaccination is the second line. So, vaccination has to be used in conjunction with biosecurity. Sometimes biosecurity is not enough to stop the spread of AI virus. When there is a large population of susceptible poultry in an area, use of inactivated AI vaccine can contribute to AI control by reducing the susceptibility of the population (Halvorson, 2004).
Consistent with the Recommendations of FAO/OIE/WHO conferences held in Bangkok and Rome, February 2004, vaccination can be used as a tool to support eradication or to control disease due to HPAI and to reduce the viral load in the environment. FAO also made recommendation for veterinary authorities to take into account the interaction between the level of challenge and the level of biosecurity of each production sector in considering the use of vaccine, as shown in the Table 1.
Sector 1 is big integrated poultry industry. Sector 2 is middle integrated poultry farm, usually integrated with sector 1, as plasma. Sector 3 is medium-small poultry farm, usually not integrated with sector 1. Sector 4 is backyard/free-rearing chicken.
Table 1. Interaction between level of challenge and level of biosecurity for different production sectors
Although vaccination program has been recommended, there is field evidence that vaccination alone will not achieve eradication, and if not used appropriately it may result in the infection becoming epidemic (Capua and Marangon, 2004).
FAO, along with OIE and WHO, recommend the following measures to fight avian influenza: “Improving veterinary services, emergency preparedness plans and control campaigns including culling of infected animals, vaccination and compensation for farmers; strengthening early detection and rapid response systems for animal and human influenza and building and strengthening laboratory capacity; and support and training for the investigation of animal and human cases and clusters, and planning and testing rapid containment activities”.
The availability and use of inactivated AI vaccine in Indonesia
There are currently 13 imported and locally produced vaccines registered for use in Indonesia, including both homologous (H5N1 seed virus) and heterologous (H5N2, H5N9 seed viruses) vaccines. Prior to registration these vaccines are tested by the National Veterinary Drug Assay Laboratory (NVDAL) for safety, potency, inactivation and purity. However, vaccines registered for use in Indonesia are currently not assessed through challenges tests for efficacy in reducing shedding of virus from birds exposed and infected after vaccination, as the NVDAL does not have the capability to do challenge tests safely.
Performance of a challenge test on each registered vaccine would allow opportunity for measurement of the amount of viral shedding post challenge, and hence allow evaluation of the ability to reduce the transmission and shedding of AI virus.
Concerns about vaccination
Concerns about vaccination for AI are known quite extensively. Most of the statements stressed that even though vaccination protects against clinical signs and mortality, reduces virus shedding and increases resistance to infection, however, the virus is still able to replicate in clinically healthy vaccinated birds.
1. Will vaccination with inactivated vaccine protect against infection or shedding?
A common objection to the use of inactivated vaccine is said to be that if a vaccinated flock is exposed to field virus, birds may be infected and shed virus (Halvorson 2004).
Laboratory results shown that vaccination eliminates or greatly reduces shedding of virus experimentally challenged birds. This table below is a challenge experiment to answer the question whether the H5N2 vaccine offered protection against the 2003 H5N1 field isolates (David Swayne 2005).
Table 2. Re-isolation of challenge virus on day 2 post-challenge
The experiment showed that after challenge of non-vaccinated birds all birds excreted virus at 2 days after challenge at very high virus titres. After challenge of vaccinated birds virus excretion was prevented in the majority of birds. In the birds, which excreted virus, the average virus titres were between 10.000 and 100.000 times less than in the nonvaccinated birds. The experiment convinced that vaccination could prevent the spreading of AI virus.
This field experience has indicated that vaccination greatly enhances a control program. There is no way a vaccinated flock can be a greater threat to disease control than a non-vaccinated flocks that breaks with HPAI.
2. Will vaccination protect against transmission?
Related to the previous concern, some have suggested that vaccinated flocks are a risk for transmitting HPAI virus to other flocks (Halvorson 2004).
Transmission experiments using H7N1 vaccine has demonstrated that vaccination not only protects chickens against disease symptoms and mortality, but is also an effective strategy to reduce transmission. Specifically, when challenged 2 weeks after vaccination, transmission of the virus is completely halted, and a major outbreak can be prevented (van der Goot, et al 2005).
Table 3. Transmission in vaccinated chickens 14 days after vaccination
All inoculated and contact chickens in the H7N1 vaccinated groups remained negative in the tracheal and cloacal swabs. This finding has shown that vaccination of poultry can be an effective tool to prevent the spread of highly pathogenic AI viruses. It should be considered to use vaccination strategy rather than stamping-out policy. That is why monitoring and surveillance program is very important.
The above experiment has shown that a non-vaccinated flock exposed to HPAI is more likely than a vaccinated flock to be a source of transmission to other flocks.
3. Will vaccine-induced antibody interfere with serology and epidemiology?
Serology is used as a surveillance tool to detect seropositive flocks. It is stated that surveillance for human cases may be becoming harder where poultry immunization is widely but inevitably imperfectly practiced as the marker of local poultry deaths for human case detection is being lost. Declines in the number of sporadic human cases in some countries such as Thailand and Vietnam should therefore be interpreted cautiously. It is also unclear as yet if massive immunization poultry programs increase or decrease the overall human population exposure to H5N1 viruses.
If vaccination is the strategy, vaccine banks should be available for immediate use and a contingency plan must be enforced. Vaccinated flock with a homologous subtype vaccine has to be regularly monitored and tested with negative results for the testing of sentinel animals, either using the haemagglutination-inhibition test (HI), the Agar Gel Precipitation (AGP) test or the ELISA test shall be used.
The ‘DIVA*’ strategy was based on the use of an oil-emulsion-based inactivated vaccine with the same haemagglutinin and a heterologous neuraminidase (N) subtype from the field virus. The possibility of using the diverse N groups to differentiate between vaccinated and naturally infected birds was achieved through the development of an ad hoc serological test to detect the specific anti-N1 antibodies (Capua, et al 2003).
Problems in government vaccination program
Although vaccination has been most widely practiced in Indonesia, it is only effectively applied in sector 1, 2 and partly the upper level of sector 3. The national strategy of blanket vaccination of all poultry is important. However, the Government plan to proactively adopt blanket vaccination of sector 3 and 4 is difficult to achieve. This can be learned and well known from the mass vaccination campaign in 2004 using 300 million doses of H5N1 locally produced vaccines.
Problems of vaccination in sector 3 and 4 poultry in affected districts are much related with the extensiveness of the coverage. Sector 4 birds are known to be difficult to catch. A commitment is needed to overcome such difficulties, and flexibility needed in developing strategies to ensure good coverage.
Issues to be addressed in each district will include engagement of the local community in sharing the objective of full coverage, the time of day to vaccinate, the persons who will conduct the vaccination, the system of payment of vaccinators to encourage commitment to full coverage, and the keeping of records regarding households where birds are vaccinated, and the numbers and classes of bird. Vaccinators have to be cleared under which authority they operate and the logistic arrangements for getting them and vaccine supplies to the
The costs of vaccination include not only purchase of product, but also designating, equipping, training, and paying vaccinators, and public education to facilitate public cooperation in achieving full coverage where vaccination is done. In the current crisis situation priority for vaccination must be given to ring vaccination 3 km radius around areas where active AI infection has been diagnosed or is suspected.
The vaccination control program should be assessed by systems of audit of randomly sampled locations. In the case of vaccination one such system is serological monitoring of the vaccinated population 3 to 4 weeks post vaccination to assess the antibody response. This program should be done by farmer and government. The Government has to develop standard operating procedures (SOPs) to undertake random sampling of vaccinated populations for serological assessment of the effectiveness of the vaccination program. We are in the right track that vaccination strategy is recognized.
1. Fighting the disease in poultry must remain the main focus of attention.
2. Avian influenza vaccination is used to complement the strict biosecurity measures and a comprehensive monitoring and surveillance programs already in place.
3. If poultry immunization is efficient and well monitored it could reduce the population burden of H5N1 in poultry and hence the risk for humans.
4. The Government of Indonesia has to proceed with the vaccination campaign, so prioritizations of areas to be vaccinated and incremental improvement in procedures are needed.
* Differentiating Infected from Vaccinated Animals
Drh. Tri Satya P. Naipospos, M.Phil, Ph.D is now a Secretary of National Commission for Avian Flu Indonesia. She played a major role in recommending the policy for Avian Flu in Indonesia with her broad knowledge on the disease. She has done numerous research on the disease along with world-class scientists in this field. She completed her Bachelor degree in 1979 from Bogor Agriculture University in 1979. She obtained her Masters degree from Reading University – United Kingdom in 1996. In 1996, she got her PhD in Veterinary Epidemiology & Economics from Massey University New Zealand. She now sits on the Directive Board at the Center for Indonesian Veterinary Analytical Studies and member of the Indonesian Veterinary Medical Association. Her research and academic writings have been published in books, journals, and newspapers.