Re: Report of a WHO working group
Re: Report of a WHO working group
EXECUTIVE SUMMARY from report with added emphasis:
Executive summary
The technology for diagnosing human H5N1 infections is mature, but many tests are
complex, some are liable to error, and some can be performed safely only in
biosafety level 3 facilities. A simple, rapid, robust and reliable test, suitable for use
in the field or at the patient?s bedside, is urgently needed.
In humans, much recent research has focused on the factors responsible for the
pathogenicity and transmissibility of the H5N1 virus. Several lines of evidence
suggest important roles for the polymerase genes, though no single gene has yet
been implicated and several genes may be working in tandem. Nor can the
distinctive age profile of this disease be adequately explained at present. A genetic
predisposition for infection is suspected based on data from rare instances of
human-to-human transmission in genetically-related persons. This possibility, if
more fully explored, might help explain why human cases are comparatively rare
and why the virus is not spreading easily from animals to humans or from human to
human.
The development of a pandemic vaccine has become more difficult following the
divergence of circulating viruses into distinct genetic and antigenic groups. To date,
results from clinical trials of candidate pandemic vaccines have not been promising,
as these vaccines confer little protection across the different genetic groups.
International standards, or "benchmarks", for evaluating the efficacy of vaccines are
urgently needed. Integrated studies of sera from individuals being vaccinated in the
various clinical trials would be equally useful ? for industry as well as for national
authorities.
Monitoring for virus resistance to antiviral drugs needs to continue. Although
resistance to amantadine is now widespread, the possibility exists that these resistant
strains may be replaced by fully susceptible strains as the virus continues to evolve.
Innovative work on novel strategies for drug development was welcomed by the
participants, but new drugs will not be on the market for some time to come.
The global picture of influenza viruses in the avian world has changed significantly
since 2002. The massive die-off of migratory birds at Qinghai Lake in mid-2005
was unprecedented, and migratory birds now appear to be contributing to
geographical spread of highly pathogenic virus. Importantly, evidence was
presented for a change in virus shedding patterns, with increased shedding from the
respiratory tract rather than the cloaca. Thus, for surveillance purposes, a
corresponding change in sampling strategies ? including both cloacal and
pharyngeal swabs ? is called for to get a true picture of the situation. Furthermore,
domestic ducks and geese ? and not chickens ? have been identified as the true
vectors of disease transmission in poultry. Recently, studies have demonstrated that
the virus is now moving both ways in relay transmission, from poultry to migratory
birds and back again. This finding might help explain some of the continuing
geographical spread.
Continued widespread infections in poultry were viewed as an important on-going
risk for human cases and the related risk of a pandemic. Participants agreed that
more needs to be done in the animal sector to control this virus. Countries with
adequate resources should continue to make culling their first-choice control
strategy; experiences in Japan and Korea have shown that such an approach, though
costly and disruptive, can ultimately be successful. In countries with limited
resources, however, the group strongly recommended use of widespread poultry
vaccination with appropriate, high quality vaccines accompanied by appropriate
surveillance to detect possible asymptomatic virus circulation. In a related
recommendation, the group suggested that countries with outbreaks should look at
the factors driving continued circulation of the virus, and then use that knowledge to
develop tailored interventions. Baseline data could be used, for example, to identify
seasons of peak virus activity and this information, too, can guide intervention
strategies. Hong Kong used this approach following the 1997 outbreak and found
that live animal markets were maintaining, amplifying, and disseminating the virus.
Intervention at this critical point eventually freed Hong Kong from the virus. More
recently, Viet Nam introduced a policy of mass poultry vaccination; human cases
subsequently ceased. Poultry vaccination is, however, recognized as having some
limitations as a control strategy, and these limitations need to be addressed on an
urgent basis: chicken immunology is much better understood than duck
immunology; ducks react differently to poultry vaccines, yet vaccines tend to be
approved based on protection in chickens only; production quality control and
antigen content of vaccines are not standardized worldwide and sub-optimal
vaccines have been used; in some countries, not all vaccine manufacturing takes
place under the control of national authorities and vaccine efficacy is not always
monitored.
Recommendations
1.
Make the development of a simple, robust, and reliable diagnostic test for use in
the field and at the patient?s bedside a high priority. Facilitate industry?s
development of such a test by providing representative panels of viruses and
addressing relevant issues of intellectual property rights.
2. Publish recommended diagnostic tests and methods for their accurate
performance, including an alert to common pitfalls, on the WHO web site, and
develop a schedule and system for regularly updating tests and kits with
appropriate reagents.
3.
Investigate the sensitivity with which currently available diagnostic tests are
capable of detecting mild or asymptomatic infections.
4. Establish benchmarks for evaluating the effectiveness of candidate pandemic
vaccines.
5. Integrate data on antibody responses in persons participating in the various
clinical trials of candidate pandemic vaccines.
6.
Determine which (if any) animal model provides the best information on crossclade
protection among H5N1 variants.
7. Continue to monitor H5N1 virus strains, in humans and avian species, to
determine changing patterns of resistance to antiviral drugs.
8.
Investigate factors that may make children and young adults especially
vulnerable to infection.
9. Conduct studies to determine whether a genetic predisposition increases the
likelihood of human infection or of human-to-human transmission among
genetically-related persons.
10.
Address and resolve the ethical issues that arise when DNA banks are
established using specimens from deceased patients, family members, close
contacts, and controls.
11.
Develop a single, agreed upon system of nomenclature to describe different
phylogenetic, genetic, and antigenic groups of H5N1 viruses globally.
12. In countries experiencing continuing outbreaks in poultry, conduct studies to
identify the factors driving continued transmission of the virus, and plan
interventions accordingly.
13. When culling is impracticable as a control strategy, introduce a policy of
poultry vaccination, accompanied by systematic monitoring, in the interest of
reducing opportunities for human exposures and infections to occur.
14. Standardize antigen content in poultry vaccines and insist on rigorous quality
control worldwide in line with OIE standards.
15. Monitor virus activity in backyard flocks and live animal markets as well as at
commercial farms.
16. Adjust sampling procedures for ducks in line with changes in the currently
recognized pattern of virus excretion, whereby more virus is now being shed
via the respiratory tract than via faeces.
17.
Continue to recognize, for the purposes of surveillance and research on
pathogenesis, the potential role of pigs (or other species) as intermediate hosts
in the generation of pandemic viruses.
18. Enhance international collaboration in the surveillance of wild birds and in the
sharing of data from such surveillance efforts.
19. Improve understanding of migratory routes for wild waterfowl and strengthen
collaborative interactions with ornithologists.
http://www.who.int/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_3C.pdf
