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Vaccinating against avian influenza

N. Gopal Raj

Vaccination has to be combined with close monitoring and increased biosecurity. Making sure that vaccinated flocks remain disease-free is essential.

AVIAN INFLUENZA (or bird flu), as its name suggests, is first and foremost a disease affecting birds. The strain of bird flu known as H5N1, which is making headlines around the world, is no exception. It is deadly to chicken and many species of wild birds, but as of now does not readily infect humans.

The highly virulent H5N1 virus spreads easily from bird to bird and from farm to farm. Infected birds shed vast quantities of the virus in their faeces and nasal secretions. According to the Food and Agriculture Organization (FAO), birds most commonly pick up the disease through direct contact with sick birds and from equipment and people's clothing that have become contaminated with droppings from infected birds. Controlling and ultimately eradicating the disease requires reducing the amount of virus circulating in poultry and on farms, observes the FAO.

Culling to remove not only diseased birds but also those that have a high risk of becoming infected remains the primary strategy for halting the spread of virulent bird flu. But after H5N1 outbreaks took hold in East Asia, it became clear that large-scale culling could cut off a major food source for rural communities and seriously damage the local poultry industry. As a result, FAO began to recommend vaccination based on a strategy known as `DIVA' (differentiating infected from vaccinated animals) for situations where mass culling was not feasible or desirable.

The DIVA strategy is based on being able to distinguish whether vaccinated birds have subsequently become infected. Vaccination can potentially result in infected birds showing no clinical signs of ill health but continuing to excrete the virus. Making sure that vaccinated flocks remain disease-free is essential so that infected birds do not spread the virus. Nor must infected birds or their eggs be used for food. Using what are known as `heterologous' vaccines provides perhaps the simplest way to implement the DIVA technique.

Influenza A viruses are classified on the basis of two proteins they carry. There are 15 subtypes of haemagglutinin (H1 to H15) and nine subtypes of neuraminidase (N1 to N9). In `heterologous' vaccines, the virus strain used in the vaccine will have haemagglutinin of the same subtype as the circulating strain of bird flu in order to raise immunity against the latter. But the vaccine strain will have a different neuraminidase type from the circulating strain so that tests can establish if a vaccinated bird subsequently becomes infected.

A FAO position paper on avian influenza explained the benefits of vaccination thus:

"If H5N1 [Highly Pathogenic Avian Influenza] virus enters a vaccinated flock it will encounter birds that have an increased resistance to infection, which reduces the likelihood of birds becoming infected. If some birds do become infected the quantity of virus they excrete is reduced, reducing the risk of onward transmission. In properly vaccinated poultry exposed to field virus, infection is highly unlikely to proceed through the flock."

The DIVA strategy was successfully used in Italy against two epidemics of low virulence bird flu between 2000 and 2003.

Subsequently, scientists in Hong Kong tested a commercial heterologous vaccine based on a killed H5N2 strain after outbreaks of the highly virulent H5N1 in 2002 and 2003. Flocks of chicken vaccinated after an outbreak remained disease-free. When chicken were vaccinated during an outbreak, the vaccine provided "significant protection of disease" and virus excretion by birds stopped 13-18 days after vaccination. In laboratory conditions where chicken were deliberated exposed to H5N1, all vaccinated chicken were protected from disease, and eight out of ten vaccinated birds did not excrete the virus. In the remaining two, virus excretion was over 1,000-fold less than when unvaccinated chicken were infected with the H5N1 virus.

"These investigations showed that the killed H5N2 vaccine, used in conjunction with enhanced biosecurity measures on chicken farms and in poultry markets, reduced the risk of H5N1 avian influenza in Hong Kong and consequently the risk of spread to humans," reported T.M. Ellis and fellow scientists at Hong Kong's Agriculture, Fisheries and Conservation Department in a published paper.

Two ways to check

With the DIVA system involving a heterologous vaccine, there were two ways to check whether a vaccinated flock had remained disease-free, according to Ilaria Capua, a leading expert on avian influenza at the Istituto Zooprofilattico Sperimentale delle Venezie in Italy. One was to have unvaccinated `sentinel' birds in the vaccinated flock and to monitor the health of those sentinels. The other was to test the blood of vaccinated birds for the presence of antibodies against the neuraminidase type of the field virus, said Dr. Capua in an email.

But for the DIVA strategy to work, vaccination had to be combined with close monitoring and increased biosecurity. Vaccination alone could not achieve eradication, and if not used appropriately it could result in the infection becoming endemic, warned Dr. Capua and a fellow scientist in a journal paper.

Late last year, China announced an ambitious programme to vaccinate all its billions of poultry against H5N1. China had approved early last year two vaccines developed by its scientists that used segments of the H5N1 virus. These vaccine strains had haemagglutinin and neuraminidase proteins similar to the infectious virus, and were said to give better protection to the birds for a longer period.

The Union Government has created a "strategic reserve" of H5 and H7 veterinary vaccines, which is kept ready near the Indira Gandhi International Airport in New Delhi. Netherlands-based company Intervet supplied the heterologous vaccine that India has stocked against H5N1, based on a killed H5N2 strain. The same vaccine was used in Hong Kong and more recently France has ordered 30 million doses of it.

The Union Government's Department of Animal Husbandry, Dairying and Fisheries has prepared an Action Plan for dealing with outbreaks of virulent bird flu, including of H5N1. When an outbreak of bird flu is confirmed, the Action Plan recommends the culling of all birds within three km of the infected farm. Vaccination could be considered for poultry in the `surveillance zone' three km to 10 km from the outbreak. The Department's protocol for access and use of vaccines for avian influenza notes that the Union Government "will decide and determine whether vaccination should be undertaken or not." This decision would be based on factors such as the nature and severity of the outbreak as well as density of the poultry population in the area and its type.

Trade in poultry and poultry products from the surveillance zone where birds had been vaccinated could be resumed after a cooling off period of about three weeks, according to the Action Plan. If no vaccination was carried out, trading could resume four weeks after all birds within the three km radius had been culled, provided no fresh cases of infection appeared in the surveillance zone.

Until recently, vaccination against bird flu viruses for the H5 and H7 subtypes was not considered or practised in developed countries as it implied export bans on live poultry and on poultry products, point out Dr. Capua and Dr. S. Marangon in a paper. In the absence of vaccination, trade bans on a given area lasted until freedom from infection was demonstrated. But with DIVA, if it could be demonstrated that the infection was not circulating in the vaccinated bird population, trade bans may be lifted, they state.

But in practice, getting trade restrictions removed after an outbreak of H5N1 can become a lengthier process with vaccination. When poultry flocks were vaccinated, then much greater surveillance and monitoring was needed to make sure that the birds remained free of the bird flu virus, observed a Delhi-based FAO expert. Resuming exports after vaccination required much documentation of all the surveillance and testing that had been carried out, he told The Hindu .

When the first outbreak of H5N1 was detected last month at commercial poultry farms in Navapur taluk in northern Maharashtra, the Central Government rushed vaccines from its stock to the State as well as to neighbouring Gujarat. In the end, it was decided not to vaccinate but to cull in the surveillance zone as well. In its notification to the World Organization for Animal Health (OIE), the Government stated, "Due to the very small number of poultry in the infected and surveillance zones, we have resorted to stamping out in the entire 10-km radius infected zone."

Subsequently, when the H5N1 infection was found to have spread from Navapur to nearby Uchachhal in Gujarat, once again all the chicken were destroyed and none vaccinated.

So as of now, no poultry flock in India has been vaccinated against the H5N1 virus. If, however, there are any more outbreaks and vaccines have to be deployed, the Central Government's reserve stock can get rapidly depleted. As each bird must be vaccinated twice for it to build up sufficient immunity, the 10 lakh doses of the vaccine the Government is said to possess would suffice to immunise five lakh birds. Many Europeans nations are now contemplating vaccinating their poultry flocks after the H5N1 virus was detected on their territory. Countries such as France, the Netherlands, and Belgium are already planning some vaccination.

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