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Id card of the new avian flu virus

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The genetic heritage of the new H7N9 influenza virus is 100% of bird origin; to this day April 16, 2013, this virus has caused 60 influenza cases and made 13 victims, at least according to official data provided by Chinese authorities. Spreading from the eastern regions around Shanghai, it has already reached Beijing. The in-depth genetic analysis of the first three cases, all of them fatal, described in the New England Journal of Medicine confirmed that all these viruses' genes, never reported before, are of avian origin.

Influenza A cases, of the H7 type, already infected humans in the past, but only one fatal case was reported in the literature, in the Netherlands a few years ago. Another one, occurred by accident in South Africa at the same time as the Chinese epidemic, was caused by an H7N1 strain. For the rest even strains pathogenic to humans have so far only caused conjunctivitis and respiratory symptoms without serious consequences. A far cry from the fatality rate of the H5N1 virus, which had so far been considered "the" avian flu virus par excellence, and according to the WHO causing since 2003, a total of 332 victims of the 566 people in which the infection had been confirmed through laboratory checks. The eyes of the experts were thus focused on the areas in which this virus is still present, and the sporadic cases in which it is transmitted to humans (the last lethal case recently occurred in Vietnam) when, all of a sudden, as usual, a new Chines strain has emerged.

The cocktail between bramblings, geese and wild birds

The genetic analysis made by the experts of the Chinese National Centre for disease control and prevention showed a degree of consistency between the three samples ranging from 99.7 per cent to 100 per cent for all the eight typical influenza viruses genes, six of which in these cases were traceable to the H9N2 virus. In addition, all three cases showed a deletion of five amino acids in the gene coding for the neuraminidase, the enzyme that facilitates the spread of the virus between cells in the respiratory system.

According to the Chinese experts who conducted the phylogenetic analysis, the new virus derives from the reassortment of genetic material between a virus that affects geese in the Yangtze River delta areas, one typical of bramblings, birds similar to finches, which are found everywhere and a virus carried by wild birds flying from Korea. The H7N9 developed from this "cocktail" and was able to infect humans. "What we still don't know is whether transmission occurs via an intermediate host, i.e. another animal in which the virus replicates before being transmitted to humans" says Yuelong Shu, who coordinated the work of dozens of colleagues in different laboratories throughout China. The authorities have repeatedly denied speculations that had at first put the spotlight on several thousand dead pigs floating in the waters that supply the Shanghai water system, the city where the first cases occurred. From an examination of some thirty of these carcases no trace of the new virus could indeed be found.

Also its ability to spread between humans so far seems dubious: for all the confirmed cases, the hundreds of people who had been in close contact with them before the onset and during the early stages of the disease, were identified and monitored. So far none of these potentially infected persons, as far as we know, has developed any symptoms.

Yet the epidemic is spreading beyond its area of ​​origin and the number of cases reported in increasing day by day. And as long as the the mode of infection remains unclear, the epidemic will be hard to stop. Preliminary data suggest that the virus should respond to the antiviral drugs oseltamivir and zanamivir, but from the genetic analysis one may suspects that resistance already demonstrated against the first anti flu drugs (amantadine and ramantidine) can easily extend to these drugs, the so-called neuraminidase inhibitors.

Synthetic biology may help in this case.

We should therefore stay on the alert. This is why, as soon as the Chinese experts, on 29 March, made the H7N9 genetic sequence available to scientists around the world through the GISAID platform a race against time has started to develop a vaccine. Indeed, let's not forget that in 2009 a few weeks delay strongly decreased the usefulness of the vaccine against the H1N1 pandemic, distributed when the peak of the infection was already waning.

Thus, in order to gain valuable time, the U.S. government has decided to take advantage of the new synthetic biology technology developed by Novartis together with the Craig Venter Institute. Before the virus samples coming from China reached the Centers for Disease Control and Prevention in Atlanta, researchers had already been able to synthesize its RNA in the laboratory, by following so to speak, the recipe of the sequence filed on the website, and had started cultivating the virus, the first step for the development of a vaccine.

The debated research which in recent months led to the production of variants of the H5N1 flu virus that can be transmitted between humans, therefore with the potential to cause an apocalyptic pandemic, will also be put to the test in practice.

Ron Fouchier, the Dutch researcher from the Erasmus Medical Center in Rotterdam who ended up in the eye of the storm a few months ago when conducting and disseminating one of these experiments, now has his say: "Through our studies we identified some conditions that allow the virus to spread between humans" he said in a telephone interview to the Washington Post. "Finding two of these five characteristics in the new virus, a few weeks after its onset, suggests that we should not underestimate it". Not least because, according to other Chinese experts that are analyzing it, the new virus is changing at a rate eight times faster than other ordinary influenza viruses.

This should not be underestimated.

According to Timothy Uyeki and Nancy Cox, of the National Center for Immunization and Respiratory Diseases at the CDC in Atlanta, the new virus also presents other pitfalls: the fact that there is no sign of illness in the birds hosting it, for example, facilitates the spread. Other genetic characteristics suggest that it may be easier for this virus to make the "great leap" to mammals , and therefore to humans.

"A crucial step is the development of diagnostic kits capable of detecting these new virus strains" added in their comment on the sidelines of the article on the New England Journal of Medicine. In China they have already developed them and are beginning to use them; the rest of the world should do the same in order to be ready in case the virus manages to "go through the border". Only in this way will it be possible to follow the virus journey and try to stop it, as well as obtain other very important data. Only by determining how many people were actually affected, will it be possible to calculate the case fatality rate of the infection, i.e. to understand whether the cases that were fatal are but a small, albeit tragic, exception, in a disease that affects thousands of people without consequences, or vice versa they indicate a much more serious situation that requires extraordinary containment measures.To date, the authorities do not believe that these are justified, so much so that the World Health Organization it not advising against travelling to or trading with China. This strategy may also depend on accusations for having caused excessive alarm in 2009, during the H1N1 pandemic. Let's hope we will not regret this prudence in the future, as this time, unlike when the SARS broke out in 2003, the Chinese authorities have been acting readily, as acknowledged by the U.S. CDC experts, and, as far far as we can say at this time, even with transparency.

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