America's North Shore Journal

The World Health Organization working group on avian flu has issued a report. Here is the 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 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.