Combating spread of H7N9 virus

By Mayo Kuo and Max Kuo 郭明裕 郭明實  / 

Sat, Apr 20, 2013 - Page 8

On April 12, the New England Journal of Medicine published a paper entitled “Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus,” detailing a study conducted by a group of researchers from Beijing and Shanghai. The paper consisted primarily of case studies of three urban residents from Shanghai and Anhui Province infected with the virus early last month, all of whom eventually died.

The research shows that the H7 component of this novel reassortant avian-origin influenza A (H7N9) virus shared the highest identity with the genes of a duck found in Zhejiang Province, and the N9 component from a migratory bird from the Korean Peninsula. Another six genetic segments had the highest similarity with migratory bramblings found in Beijing. This strain seems less virulent than its H5N1 cousin, and the symptoms in infected children are relatively mild. Infected adults could develop diarrhea, encephalitis, rhabdomyolysis, where damaged muscle tissue breaks down and is released into the bloodstream, and severe acute respiratory distress syndrome.

Nevertheless, the low white blood cell count was either normal or only slightly decreased, and not as low as observed in patients infected with H5N1; neither was a low platelet count prevalent, all of which is consistent with low pathogenic avian influenza (LPAI).

The Q226L section of the H gene in this H7N9 strain of the avian flu virus suggests a mutation, giving it an enhanced ability to bind to mammalian-like upper respiratory tract receptor cells.

There have been other mutations, such as a part identified as the E627K substitution in the PB2 protein, which has also been associated with mammalian adaptation and respiratory-droplet transmission.

The 292K gene mutation in the N gene is indicative of the fact that the virus has started to present lab resistance to the oseltamivir — marketed as Tamiflu — treatment, although the ineffectiveness of Tamiflu in clinical treatments was due to the fact that the drug was administered too late, by which time the virus had already decimated the pulmonary alveoli and caused multiple organ failure in the host.

Given that the number of cases is slowly increasing, at an arithmetic rate, and the death rate is relatively high, we see that while H7N9 is, indeed, an avian — and quite possibly specifically a duck — influenza, it is now also attacking middle-aged people and, in some cases, the elderly, the genes having mutated so that the virus can bind to receptor cells along the upper respiratory tract in humans and can be transmitted via respiratory droplets. In addition, the signs are increasingly pointing to a mammalian intermediary host.

Another article was published in this same edition of the New England Journal of Medicine, written by Timothy Uyeki and Nancy Cox of the US Centers for Disease Control and Prevention, which supported the view that the virus had, to a certain degree, mutated so that it could infect mammals.

And yet, the authorities in Shanghai were satisfied with a number of poultry testing positively for the H7N9 virus, as if they were unaware that chickens are not mammals, and that pigs are.

As the H7N9 strain is not yet being transmitted human-to-human in large numbers, it is not yet economically viable to develop a vaccine, especially given the lessons learned from attempts to create vaccines against the H5N1 strain.

The antibodies in the H5N1 vaccine reported in the March 30, 2006, edition of the New England Journal of Medicine, for example, were found to be ineffective, requiring six-fold strength doses, twice administered, before even a slight effect was observed. In addition, there is the poor performance of the antibodies produced in the vaccine against H7 sub types noted in the above study.

Instead, it might be better to pay attention to the importance of monitoring the genetic reassortant of avian influenza that results from the next migration of wild fowl from the Korean Peninsula to Zhejiang Province in China, and from there to the Taiwan coast.

Mayo Kuo is a Taiwan-based pediatrician; his brother, Max Kuo, is a US-based pediatrician.

Translated by Paul Cooper