April 25, 2013

Avian Influenza A(H7N9): Full Genetic Sequence Publicly Available

The avian influenza A(H7N9) virus (official name) has emerged in China since February, and human cases of infection have increased steadily and spread to Taiwan. Of 112 cases reported, there are 22 deaths; China Daily updates; map of cases here. Just yesterday, the World Health Organization (WHO) issued this characterization: “This is an unusually dangerous virus for humans," said Keiji Fukuda, assistant director-general for health security of WHO. The true pathogenicity of the virus in humans is unclear; some reports state a mortality rate of 20% (deaths/cases); however, this is inexact because there may be mild disease that is not detected, and the actual lethality may be lower. The virus is avian in origin, a triple reassortant (mixture) of three avian viruses. Initial assessments are that humans are acquiring infection through contact with infected birds; the unanswered question is whether human-to-human transmission is occurring (a precursor to a true pandemic). H7N9 has been sequenced and genetic analysis reported by two groups, one from China and one an international collaboration, which noted: “These viruses possess several characteristic features of mammalian influenza viruses, which are likely to contribute to their ability to infect humans and raise concerns regarding their pandemic potential.” Since the outbreak originates from China, the level of transparency from this country is critical and so far, reports are positive. WHO has reported that it receives case notifications from Chinese public health officials, and that China has sent virus samples to all 5 international collaborating centers for influenza (which includes the U.S. Centers for Disease Control (CDC)).The virus genetic sequences (sequences of the coding regions of all eight viral genes) were deposited in the influenza sequence database maintained by the Global Initiative on Sharing All Influenza Data (GISAID). This is a global consortium that was started after the 2004-5 influenza A(H5N1) outbreaks, amid concerns that virus sequences were not being shared, due to concerns about asymmetry between virus sharing and access to antivirals and vaccines, particularly from developing countries (e.g., Indonesia withheld H5N1 viruses). Claims for patent rights surfaced in the H5N1 pandemic, including a patent application filed by the CDC (see here for my article on the set of patent rights relevant to influenza pandemics). Despite the fact that patent rights have been sought for H5N1 virus sequences and H1N1 virus sequences, the sensibility of GISAID is to encourage unrestricted access: 
Influenza viruses have not been subject to intellectual property rights historically. This tradition has been important because the required changes in influenza viruses contained in human influenza virus vaccines to match those viruses circulating currently in the field must occur at a speed far in excess of the legal process associated with the attainment of commercial protection. In order to allow rapid development of products such as vaccines and other interventions on an equitable basis by all countries and other interested parties, the convention has been for human health professionals to share virus specimens and data openly without creating barriers of exclusivity such as the filing of patents. 
Already, this public health crisis illustrates a strikingly different posture by China in contrast to its reaction to the emergence of SARS (Severe Acute Respiratory Syndrome) in 2003, most notably in transparency. During that period, China was not initially forthcoming with the details of the epidemic, and the absence of information impeded public health surveillance. When SARS appeared, the causative agent was not immediately known and it was finally identified as a novel coronavirus. In addition to the difficulties on obtaining actual epidemiological data during the crisis, the SARS crisis was also encumbered by the efforts of leading research groups to file patent applications on the SARS virus sequence. With respect to influenza viruses in general, progress in linking the sharing of virus genetic sequences to access to countermeasures (overcoming some of obstacles in the H5N1 pandemic) has occurred with the establishment in 2011 of the Pandemic Influenza Preparedness Framework Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits (PIP) by WHO, which applies to influenza viruses with pandemic potential. PIP thus encourages the dissemination of virus samples and research results; it also provides for transparency in virus sequence tracing by contributing laboratories, and it embeds norms which discourage seeking intellectual property rights (but this is not legally binding). As PIP is recently enacted, it has yet to be tested in a declared pandemic, and it is not clear that the current H7N9 outbreaks will amplify into an official pandemic. 

One other aspect of H7N9 is notable at present: the virus genetic sequence has two mutations linked to increased human-to-human transmission which were identified in the H5N1 research papers that were subject to debate in late 2011 as possible sources of dual-use information (the debate centered on whether the data should be published). For background, see here and here. The question: what does the observation of these mutations mean for the viability (and scientific merit) of the earlier dual-use experiments? Has their utility been increased as a result of what is being learned about H7N9? 

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