Monday, January 15, 2018

PLoS One: Effectiveness of HPAI H5N1 Vaccination in Poultry - Indonesia


With H5N6, H5N8, H5N1 and an array of lesser HPAI H5 viruses continuing to expand globally we've seen desperate pleas from some hard hit farmers to allow the use of poultry AI vaccines (see South Africa: DAFF Statement On Vaccines For Avian Flu and USDA Issues 2nd Request for Proposals for HPAI Vaccine)
With the exception of China, Egypt, Indonesia, Vietnam, and Hong Kong, most countries eschew the use of bird flu vaccines, and opt instead for the OIE recommended course of culling and containment.
The reasons run the gamut from fears that poultry vaccines may only mask bird flu - not prevent it - to concerns over selling vaccinated  birds to foreign markets.  Once vaccinated, antibody tests would show positive titres, whether the birds were infected or not.

Reasons why, for more than a decade, the OIE has warned that vaccination of poultry cannot be considered a long-term solution to combating avian flu. And that “Any decision to use vaccination must include an exit strategy, i.e. conditions to be met to stop vaccination. – OIE on H7N9 Poultry Vaccines.

Countries that have gone the vaccine route over the past dozen years haven't found an easy way to that `exit strategy' - and while vaccine use may have them spared some economic pain - avian influenza has become increasingly entrenched in their poultry industries. 

The problem is that as avian viruses evolve, poultry vaccines become increasingly less effective; often only masking the symptoms of infection.
As an example, a 2012 study (see Egypt: A Paltry Poultry Vaccine), examined the effectiveness of six commercially available H5 poultry vaccines used in Egypt; only one (based on a locally acquired H5N1 seed virus) actually appeared to offer protection.
Poor vaccine matches can allow AI viruses to spread silently among flocks, to continue to reassort and evolve, and potentially lead to the emergence new subtypes of avian flu. A few earlier blogs on that include:
Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China).

Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens

EID Journal: Subclinical HPAI In Vaccinated Poultry – China
We've a new study, published late last week in PLoS One, that looks at the effectiveness of HPAI H5 vaccination in Indonesia, a country once known as the world's hot spot for human H5N1 infection, but now (for reasons cloaked in mystery) has fallen off that list. 
Since Indonesia declared bird flu `endemic' in 2006, they haven't had to make regular OIE reports - and so like from Egypt - we get relatively little solid reporting on their bird flu struggles in recent years. 
Today's report, however, paints a less than impressive picture of poultry vaccination effectiveness in Indonesia over the past decade. The authors cite frequent low HI titres in poultry even after three rounds of vaccines, vaccination failures, and warn of silent infections and the generation of new H5N1 antigenic variants. 
While the authors recommend steps they believe would improve Indonesia's AI vaccine performance, the upshot is that effective poultry vaccination programs have been elusive in Indonesia even after a decade of use, and are far more complex to mount than most people believe.
I've only included some of the highlights from a much longer study, follow the link to read the paper in its entirety.
Field effectiveness of highly pathogenic avian influenza H5N1 vaccination in commercial layers in Indonesia 
Simson Tarigan ,Michael Haryadi Wibowo,Risa Indriani,Sumarningsih Sumarningsih, Sidna Artanto, Syafrison Idris,Peter A. Durr, Widya Asmara, Esmaeil Ebrahimie,Mark A. Stevenson,Jagoda Ignjatovic
Although vaccination of poultry for control of highly pathogenic avian influenza virus (HPAIV) H5N1 has been practiced during the last decade in several countries, its effectiveness under field conditions remains largely unquantified. Effective HPAI vaccination is however essential in preventing incursions, silent infections and generation of new H5N1 antigenic variants. 

The objective of this study was to asses the level and duration of vaccine induced immunity in commercial layers in Indonesia. Titres of H5N1 haemagglutination inhibition (HI) antibodies were followed in individual birds from sixteen flocks, age 18–68 week old (wo).
The study revealed that H5N1 vaccination had highly variable outcome, including vaccination failures, and was largely ineffective in providing long lasting protective immunity.
Flocks were vaccinated with seven different vaccines, administer at various times that could be grouped into three regimes: In regime A, flocks (n = 8) were vaccinated two or three times before 19 wo; in regime B (n = 2), two times before and once after 19 wo; and in regime C (n = 6) three to four times before and two to three times after 19 wo. HI titres in regime C birds were significantly higher during the entire observation period in comparison to titres of regime A or B birds, which also differed significantly from each other. 

The HI titres of individual birds in each flock differed significantly from birds in other flocks, indicating that the effectiveness of field vaccination was highly variable and farm related. Protective HI titres of >4log2, were present in the majority of flocks at 18 wo, declined thereafter at variable rate and only two regime C flocks had protective HI titres at 68 wo. 

Laboratory challenge with HPAIV H5N1 of birds from regime A and C flocks confirmed that protective immunity differed significantly between flocks vaccinated by these two regimes. The study revealed that effectiveness of the currently applied H5N1 vaccination could be improved and measures to achieve this are discussed.
HPAI vaccination, intensively applied in Sector 3 layers in Indonesia, had highly variable outcome, including vaccination failures and did not provide sufficiently long protective immunity in the majority of flocks. Indonesia adopted HPAI vaccination in 2004 with the aim of reducing the incidence of H5N1 infections in poultry, with the ultimate objective of achieving eradication of the virus.
Assessment of field effectiveness of the currently applied H5N1 vaccination was useful in demonstrating that vaccination, as practiced in Sector 3 poultry, could be improved. In particular, we have identified that the most frequently used vaccination regime, consisting of three vaccinations before 19 wo, does not provide sufficiently long lasting immunity and protection of layers with any of the commonly used HPAI vaccines.
Instead, four or five vaccinations, of which two are during the laying period at 26–28 and 40–48 wo, would ensure longer lasting protection and further reduce the risk from exogenously introduced H5N1 infections. Monitoring the level of immunity in vaccinated flocks would help to identify key factors that contribute to inadequate responses to vaccination, short duration of protective immunity and vaccination failures. The timing of re-vaccination could be adjusted according to the flock immunity, ensuring an effective response and longer lasting protective immunity.
(Continue . . . )