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Im folgenden die wissenschaftliche Bewertung einer Impfaktion in Hongkong, durchgeführt vor einigen Jahren. Die Impfung erfolgte in einem zeitlich und geographisch eng begrenzten Rahmen.
Nachdem einige der oben angesprochenen Aspekte thematisiert werden, stelle ich einen grösseren Teil des Papiers ungekürzt ein.
Nachdem einige der oben angesprochenen Aspekte thematisiert werden, stelle ich einen grösseren Teil des Papiers ungekürzt ein.
Vaccination of chickens against H5N1 avian influenza in the face of an outbreak interrupts virus transmission
Trevor M. Ellis1,+, Connie Y. H. C. Leung2, Mary K. W. Chow3, Lucy A.
Discussion
One of the concerns in the use of vaccine to control HPAI in poultry farms is the possibility that while vaccine may protect from disease, asymptomatic virus circulation may continue, resulting in spread of infection to other farms. The monitoring and surveillance conducted on these three chicken farms showed that use of this killed H5N2 vaccine in the face of HPAI H5N1 virus challenge was able to protect chickens from disease and interrupt virus transmission. The protective effect of vaccine became apparent after day 18 post-vaccination. On farms 1 and 2, clear evidence of H5N1 infection was demonstrated in sheds of vaccinated chickens,and subsequently extensive surveillance by clinical inspection and virus detection tests, both H5 RRTPCR and virus culture, showed that the virus transmission had been interrupted. For farm 3, the rapid depopulation of the affected shed and strict biosecurity measures applied combined to minimize the level of challenge to other sheds. No evidence of clinical disease or H5N1 infection was demonstrated in the sheds of vaccinated chickens so it is possible that the other sheds on this farm may not have received significant exposure to the H5N1 virus from the initial infected shed. Vaccines have been used in other countries to assist in the control of avian influenza. Countries that have used vaccines for avian influenza control include Italy (Capua et al. , 2002), the US (Halvorson, 2002), Mexico (Villarreal & Flores, 199 and Pakistan (Naeem, 199. Mostly vaccination has been directed against low pathogenic strains of avian influenza virus but Mexico and Pakistan have successfully used vaccine against highly pathogenic H5 or H7 avian influenza viruses. Experimental studies have shown that commercially available H5 avian influenza vaccines could protect poultry from 1997 Hong Kong strains of H5N1 HPAI virus (Swayne et al ., 2001). On Farm 2, avian influenza H9N2 virus was detected in the sheds containing 16-day-old to 32-day-old chickens. Recent experimental studies have suggested that infection with H9N2 virus may stimulate cell-mediated immune responses that could cross-protect chickens from intranasal H5N1 virus challenge that was lethal in uninoculated controls (Seo & Webster, 2001). This crossprotectivity was effective at 15 days after intranasal inoculation with H9N2 virus given in a low challenge dose (10 50% lethal chicken doses), but its effectiveness was diminished by 30 days postinoculation. Infection of chickens with H9N2 avian influenza viruses is quite common in chickens in Hong Kong based on monthly serological surveillance conducted by our laboratories on local and imported chickens between 1999 and 2001. The H9N2 viruses isolated from chickens in Hong Kong belong to a lineage of viruses related to A/ Duck/Hong Kong/Y280/97 (H9N2) (Guan et al., 2000), which generally causes mild or inapparent infections of the upper respiratory tract in chickens. On local farms where H9N2 infection has been monitored, it generally occurs in chickens under 30 days that are reared on litter. By the time they are moved to the A-frame cages infection is less common and chickens of multiple ages on affected farms are H9N2 antibody positive. On farm 2 with H9N2 infection circulating in the 16-day-old to 32- day-old birds it would be highly probable that the older birds (39 to 46 days old) in sheds 1 and 3 would have been exposed to this virus, but this did not prevent the H5N1 outbreak in these sheds. During the 2002 H5N1 outbreak on chicken farms in Hong Kong there appeared to be no correlation between exposure to H9N2 virus, measured by serology, and the severity of the outbreak. The H9N2 AI virus exposure and resulting immunity had no protective effect against the field challenge by H5N1 AI virus possibly because of either shortlived shortlived cross-protective cellular immunity or a high environmental challenge dose of H5N1 AI virus. Avian influenza vaccination has generally been used in uninfected flocks in control areas around but not including infected flocks. From this investigation we are definitely not suggesting that the use of vaccination to assist in the control of an avian influenza outbreak could be delayed in the control area until evidence of spread from infected farm(s) occurs. Nor do we recommend the use of partial depopulation plus vaccination on an infected farm as a normal practice. In the first Tai Kong Po farm, five sheds with 22 000 chickens had to be killed before vaccination had a chance to work in the final shed, and in the meantime outbreaks occurred on two nearby farms that were ring vaccinated at the same time as the initial farm. Generally, when ring vaccination is used for avian influenza control, the infected farm and highrisk contact farms within an epidemiologically sustainable perimeter (usually several kilometres) are quarantined, monitored and possibly depopulated. Ring vaccination is used outside this zone where there is a good chance for immunity to develop to the virus before exposure occurs. The close proximity of farms and limited land availability makes this approach difficult in Hong Kong. For the three farms involved in this investigation the individual circumstances at the time, together with expanding use of preventative vaccination throughout Hong Kong, led to an unusual control strategy involving quarantine, partial depopulation and vaccination of unaffected sheds and surrounding farms. As part of this strategy very strict attention had to be paid to movement control of birds, people and materials onto and from the farm and strict biosecurity practices had to be maintained. This was combined with an intensive monitoring programme on the vaccinated sheds and the surrounding farms to rapidly detect any spread of the infection. This strategy was very resource intensive and would have been very difficult to sustain in a more widespread outbreak. Another factor that should be considered with vaccinating in the face of an outbreak is the possibility of selection of variant viruses when the virus is replicating rapidly in the presence of partial or incomplete flock immunity. The chance of this occurring will clearly be lower if virus is introduced to a fully vaccinated flock that has had time to develop its immunity. However, concerns expressed about the risk of enhanced H5N1 virus evolution in the presence of a vaccinated antibody-positive chicken population needs to be kept in perspective. If you do not vaccinate, all exposed chickens have the potential to become infected with H5N1 viruses that will replicate to high titres and shed large quantities of virus in faeces and respiratory secretions that will infect further chickens. Each replication cycle increases the number of mutations and 410 T. M. Ellis et al.
the potential for antigenic variation. There are also many examples of emergence of HPAI avian influenza viruses from low or medium pathogenic avian influenza viruses without any influence from vaccination (Alexander et al., 2000). Inactivated oil emulsion avian influenza vaccines have given good protection despite variation of up to 10.9% in haemagglutinin-deduced amino acid sequence (Swayne et al., 1999, 2000). Avian influenza vaccination has been most widely practiced in Mexico, beginning in January 1995, and it continues to be used. Over 1.4 billion doses of inactivated vaccine and 500 million doses of fowlpox-AI-H5 recombinant vaccine have been used and the vaccines are still considered protective (Villarreal-Chavez & Rivera-Cruz, 2003). The ultimate goal of any control programme for avian influenza should be to eradicate HPAI. This was also the goal in Hong Kong during this outbreak, and this goal was achieved. With the presence of these viruses in wild water birds in the region and the large daily cross-border movement of poultry the risk of H5N1 virus incursions infection in Hong Kong is very high. A comprehensive package of measures including enhanced biosecurity programmes for farms, wholesale and retail poultry markets, the use of rest days in markets to break cycles of infection and a comprehensive monitoring and surveillance programme for early detection of any H5 avian influenza virus incursions have been in place since 2001 and were enhanced after the February to April 2002 outbreak. As stressed by international animal health authorities (Alexander et al ., 2000), avian influenza vaccination in Hong Kong is used to complement the strict biosecurity measures and a comprehensive monitoring and surveillance programme already in place. Comprehensive vaccination of all chicken farms supplying the local retail markets was introduced as an additional layer of protection after a one year long vaccination evaluation trial (Ellis et al., 2004b). This investigation showed that the use of killed H5N2 vaccine on three farms undergoing H5N1 HPAI outbreaks was able to protect chickens against disease and also to interrupt asymptomatic virus shedding. This is particularly relevant when dealing with viruses such as H5N1 where the virus also poses a significant risk to human health.
Acknowledgements The authors thank the staff of the Avian Influenza Serology, Avian Virology, Molecular Biology, Histology and Bacteriology laboratories at Tai Lung Veterinary Laboratory, the staff of the Department
of Microbiology, University of Hong Kong and the field staff of Livestock Farm Division for their excellent technical support. The studies at The University of Hong Kong were supported by The Wellcome Trust Grant 067072/D/02/Z and a Public Health Research Grant AI95357 from the National Institutes of Allergy and Infectious Diseases.
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