The much-awaited springtime seems to have an unfortunate knack for bringing us scary diseases. Almost exactly ten years ago, surgical masks were à la mode, and the World Health Organization was reacting to the outbreak of what we now know as Severe Acute Respiratory Syndrome, or SARS. Four years ago this month, we were working hard to track and stop the spread of the 2009 H1N1 pandemic swine flu.
Today, the public health and medical worlds are faced with not one, but two emerging diseases: the novel coronavirus, and avian influenza H7N9 – a virus previously only seen in animals.
We are rapidly learning a lot about both of these viruses. Yet, there is one key fact that remains unknown: what is transmitting this virus to humans? What is the reservoir for this virus?
As previously reported, on March 31, three cases (including two deaths) of H7N9 were confirmed in Shanghai and Anhui Province, China. These marked the first documented cases of human H7N9.
Since March 31, the case count has steadily increased up to 16 cases including six deaths. The latest cases, a 61-year-old woman and a 79-year-old man from Nanjing, were reported this morning (EDT). Sixty-five contacts are now under surveillance – officials are looking for abnormal symptoms and evidence of human-to-human transmission.
As Canadian reporter Helen Branswell explains, through genetic sequencing of this virus, scientists know that all the genes are avian, but it’s a bird flu virus that knows how to adapt to mammals – specifically, humans. The WHO suggests not only that this virus can bind to human cells, but it can also grow at temperatures close to the human body temperature.
Yesterday, the Chinese Ministry of Agriculture revealed that strains of H7N9 that bore serious resemblance to the H7N9 infecting humans, were found in pigeons in Shanghai. In an encouraging sign of transparency, the Chinese government promptly reported the finding to the OIE (the world health organization for animals). As a result, Shanghai officials are ordering the slaughter of poultry.
Influenza infects and spreads in different animals. Birds, pigs, dogs, horses, and aquatic mammals (seals and whales) can all be infected and sick with the flu. Let’s review. There are three different types of influenza: A, B, and C. Influenza A can be broken down into subtypes differentiated by the proteins, hemagglutinin and neuraminidase, that are found on the virus. Some of these different subtypes are influenza A H1N1, H3N8, H3N2, H5N1, and the now famous H7N9. These subtypes can be broken down into different strains. For example, there are different strains of H1N1.
Different subtypes of the virus can infect and cause disease in different species. Birds, according to the WHO, provide a vast reservoir for influenza A viruses. One of the most concerning is H5N1. H5N1 historically only infected birds, but in 1997, there was an outbreak among humans in Hong Kong. The virus reemerged in people in 2003 and 2004. Since 2003, about 387 people have been infected with H5N1 and 245 have died. The good news is that this virus is not well adapted to humans, so human to human transmission is rare, at least for the moment. If there is no sustained human-to-human spread of H7N9, this virus could prove similar to H5N1. In the rare case when human-to-human transmission of H5N1 was suspected, it was typically in a small cluster. Clearly, we will have to continue careful monitoring of the spread of H7N9.
So why is it called ‘avian influenza’ or ‘swine flu,’ yet, people get sick? Welcome to Reassortment 101. When someone becomes sick with influenza, the influenza virus is actually latching on to the human host cells and hijacking their DNA to allow itself to replicate. Once the virus is replicated, it leaves the cell to infect other cells. Reassortment can occur when a host is infected with more than one influenza virus at a time, and some of the influenza virus RNA segments mix together. So, when the new influenza virus – that which has been produced inside the human host cell – is ready to bust out and infect other cells, it can be a combination of segments from two different influenza viruses.
The likelihood a host will be infected with two different influenza viruses depends on the host and the influenza viruses circulating. This is where pigs come in. Pigs are susceptible to infection from both avian and human influenza viruses, making them a playground for segment-swapping viruses. Both human and avian influenza viruses require the existence of very specific cells to bind to, if they are to cause infection. Mammals don't have the binding or “receptor” cells that birds do, and vice versa. However, pigs have both of these receptor cells in their respiratory tracts. Pigs can either serve as an intermediary host, transmitting influenza from one species to another, or they can serve as a “mixing vessel,” where influenza viruses reassort and new viruses (reassortants) emerge.
The bottom line is that we should take the flu far more seriously than we do. It is an immensely tricky virus that is prone to change and therefore a constant challenge to vaccine producers. We have seen influenza viruses change in the past and cause outbreaks both mild and quite serious (2009 H1N1 pandemic). H7N9 is typically a low pathogenic virus in birds, meaning that if it in infects birds, it causes a mild illness that is not very obvious. This makes it hard to know how common it is in China’s healthy appearing birds.
It seems to be more pathogenic in humans, but we can’t say for certain. As Branswell points out, flu illness follows a certain pattern in people: there are a few severe and fatal cases, and loads of sick people with mild illness that may not even know they have the flu. For the most part, people stick out the illness in bed, without giving it a second thought. So, we should remember that the cases we are counting now, do not necessarily represent the whole spread of this virus. There could be very mild cases not being diagnosed. If that is the case, maybe the virus is not as severe as it seems. Also, it could suggest that something different about how it spreads.
People infected with H7N9 are presenting with severe pneumonia. The WHO recommends that people wash their hands. All the time, and then again. No travel or trade restrictions have been issued for China.
There is currently no vaccine for H7N9, but experts are debating the development of one. Reuters reports that creating an H7N9 vaccine would be at the expense of seasonal flu shots. One of my professors famously stated that public health is “The art and science of deciding who dies, when, and with what degree of misery.” Public health policy decisions are based on maximizing the overall public health, but there is now way to protect everyone from everything. The seasonal flu may not be serious for most of those infected, but every year between 3,000 and 49,000 Americans die from the flu. Experts are working to learn more about the biology of the virus, and H7N9’s potential to cause a pandemic so that they can make fully informed decision on vaccine manufacturing
There is no specific treatment, either, but the WHO states that H7N9 is susceptible (vulnerable) to certain drugs such as oseltamivir and zanamivir.
In the meantime, enhanced surveillance for unexplained pneumonias, epidemiological investigations of the contacts of cases and animal health investigations are being conducted.