Analysis: Mexico’s avian flu vaccination experience

Movement of live birds and manure contributed to the rapid spread of avian influenza in Mexico and the disease has persisted in layers spite of extensive use of vaccination. 
High bird mortalities from avian influenza were first reported in Jalisco, Mexico, on June 9, 2012. "We all thought it was necessary to proceed with timely, fast, reliable and immediate diagnosis, followed by sacrifice, quarantine and control of the movement of products and by-products, especially of live birds,” said Dr. Miguel Angel Marquez, independent consultant, and United Nations Food and Agriculture Organization (FAO) and World Organisation for Animal Health (OIE) consultant. But this was only the beginning.


Mexico chooses vaccination
With the rapid advance of the outbreak, many poultry producers were at risk of losing their livelihoods, and this led to an outcry for vaccination. But, support for avian influenza vaccination was not universal. The OIE approved means of dealing with foreign animal diseases, like highly pathogenic avian influenza, is eradication. But with the loss of millions of birds, the Mexican government together with the National Association of Poultry Sciences in Mexico (ANECA), CONASA, the advisory body for SAGARPA (the Ministry of Agriculture and Rural Development, Fisheries and Food) and other experts concluded that vaccination was the only way to stop the spread of the disease.
In the avian influenza outbreak of 1995, Mexico was widely criticized by the international community for proceeding with vaccination. Although it caused a lot of controversy at the time, the OIE itself finally accepted it. Mexican poultry producers believed that the extent of the outbreak in 2012 once again required vaccination.
"Definitely, my opinion is that the use of the vaccine has been positive. As you may recall, Mexico was the first country to use a vaccination strategy in 1995 when faced with the outbreak of subtypes of avian influenza, and the OIE recommended sacrificing birds," says Dr. Eduardo Lucio, director of IASA, a producer of an avian influenza vaccine.
If birds are not vaccinated, they must be euthanized to prevent the outbreak from spreading. But in Mexico, the spread of the virus was due to the movement of live birds and manure. When the avian influenza outbreak got out of hand, vaccination was seen as the only solution.
Vaccination makes surveillance for the virus more difficult, because antibody tests can’t distinguish between vaccinated and infected birds. "This is the reason why our authorities and the international organizations opposed the vaccination, but when the problem took such proportions, the same authorities and international organizations had no choice but to accept it,” says Dr. Marquez.


Which vaccine to use?
To develop an inactivated oil-emulsion vaccine, a low pathogenicity seed virus is necessary. The challenge is that the vaccine is needed immediately, but its preparation takes about a couple of months.
Fortunately, Mexico had a low pathogenic duck H7N3 virus isolated in 2006 that saved the industry. The National Health Service Food Safety and Quality (SENASICA) ran tests and showed a homology of more than 90 percent to that of the Jalisco virus. The vaccine was manufactured via a fast track. Within 21 days the first doses were administered and the vaccination proceeded, reportedly with great success. The duck virus initially protected adequately, however, this was almost three years ago.


Hypervaccination for avian influenza
During the past three years, due to the many replications of the field virus in unvaccinated and vaccinated hens, the Jalisco and Puebla viruses have accumulated changes in their amino acid sequences, so the homology between the field strain of virus and the vaccine has been reduced.
In fact, Dr. Lucio said, "Work reported in 2002 by Dr. David Suarez, research leader, USDA Southeast Poultry Research Laboratory, suggests that the H5N2 vaccine was not effective enough and there was a need to change the seed vaccine." Similarly, "Observations carried out on H7N3 virus populations indicated the same problem. This data was also shared in 2013 with the health authorities and some members of the UNA (National Poultry Union of Mexico)".
Now both poultry producers and the veterinary community in Mexico are asking for a vaccine made from another virus, but it has not been authorized. "When you have an updated seed,” explains Dr. Eduardo Lucio, "the field virus replication is much lower.”
One drawback is the current practice of hypervaccination. Breeding and laying hens receive up to five vaccinations between the period of hatching and development into adulthood (20 weeks old). Despite this, they are poorly protected. The hypervaccinated flocks become infected when exposed to the avian influenza virus, leading to low production and some mortality.
Dr. Marquez said, “The ideal would be to have an updated vaccine that would help to reduce low production and mortality in vaccinated caged hens." This is also true for recombinant vaccines because if the recombinant virus hemagglutinin is not modified, the vaccine loses ability to control the circulating virus populations.
The oil-emulsion inactivated vaccine, subcutaneously or intramuscularly injected, produces humoral antibodies in birds. Hypervaccinated flocks have very high antibodies in the bloodstream, but they do not have immunity in the epithelia of the respiratory and gastrointestinal tracts (i.e. no mucosal protection). Thus, the current pathogenic field virus challenges and colonizes hypervaccinated birds. Field virus is then replicated and excreted. This would not be the case if the seed virus was updated.
"The first thing to do is to have an updated vaccine and to reapply all biosecurity measures and enforce the law with full force on the mobilization of birds," adds Dr. Marquez.


Legal framework in Mexico and the world
Everything indicates that the regulation is aimed at defining the requirements for the use of a highly pathogenic vaccine. However, the Mexican veterinary pharmaceutical industry is awaiting health authorities to allow timely update of the seed. "Today we have an outdated legal framework, where there is still an official (controlled) seed, which makes efforts by companies to efficiently satisfy farmers very difficult," says Dr. Lucio.
The legal framework is unsuitable. "It should be very similar to that used in the case of human influenza vaccines, where the laboratories that produce these vaccines must update their vaccine seeds every year.” “This way,” continues Dr. Lucio, "a very similar regulatory framework should be made, if not identical, because we are talking about the same virus."
The in-depth review of the regulatory framework is not only in Mexico, but also from international bodies such as OIE. The OIE has no Mexican reviewers in the Ad Hoc Group. "Mexico and China are the two countries with the greatest experience in the use of vaccines that could greatly contribute to the current context of how they should be used as tools for eradication," says Dr. Lucio.


Manure movement a problem
According to experts, the three main sources of avian influenza virus spread in Mexico are listed below in order of importance:
1.            Transport of hen manure without proper heat treatment and used as fertilizer on farmland.
2.            Transport of chicken manure without heat treatment for cattle consumption.
3.            The transport of second-cycle live birds or infected birds, or birds that may still be spreading the virus through excretions both in feces and respiratory secretions.
In March 2014, poultry manure transport was banned in the states of Jalisco and Puebla, but compliance is not fully followed. Dr. Marquez said, “The authorities cannot be vigilant for truck farms in outbreak areas 24 hours a day.” There must also be cooperation from poultry producers. The same applies to road transportation of vaccinated hens which may be carrying the virus heading South and Southeast to be molted.


The experience in Mexico and impact in the US
Dr. Lucio said that American poultry producers can learn from the Mexican experience of what kinds of vaccines to use via different vaccination schedules. Dr. Lucio said, "It took us time to realize that it is necessary to consider an update of the vaccine seed. Therefore, our vaccination strategy has not been as effective as it should've been.”
Mexico is not alone. There have been cases of avian influenza outbreaks in Italy, China and Egypt all controlled with updated seed vaccines. These concepts are not clearly documented in the recommendations of the OIE.