Disease Monitoring丨EV-A71 is no longer the main pathogen of severe hand, foot and mouth disease, so is it still necessary to get the vaccine?

Last Friday, the Chinese Center for Disease Control and Prevention published a paper (see the picture below) with Director Zhang Yong as the corresponding author, which highlighted that some issues that need attention were found through sequence analysis of the "VP1 structural protein" (remember this word) of Coxsackie A6 (CV-A6), but the conclusion is this:

CV-A6 monitoring needs to be improved (there are more undetected samples, Figure D below), and there is a risk of "outbreak".

So how should the general public understand this conclusion?

In fact, the general public does not need to pay too much attention to this information, because this is a very forward-looking study. Its purpose is to combine the current epidemic trends of hand, foot and mouth disease pathogens (enterovirus, including coxsackievirus, enterovirus 71, echovirus, etc.), focusing on the potential threats of "high proportion of severe cases" and "pathogens not covered by vaccines".

You should know that in 2008, the outbreak caused by enterovirus 71 (EV-A71) was first reported in Fuyang, Anhui, my country (see the picture below, initially described as a "mysterious virus"). In just over two months, thousands of children were hospitalized in Fuyang alone and more than 20 children died. The diagnosis of several early cases was not "severe hand, foot and mouth disease" but "lung infection."

Why did the pathogen (EV-A71) that has existed for a long time and causes a low-harm, self-limiting disease (hand, foot and mouth disease) suddenly change its form, causing so many children in a city to become ill, hospitalized, and even seriously ill and die? It even pushed the country to include hand, foot and mouth disease in the "notifiable infectious diseases"?

The reason is also related to "insufficient monitoring" that year.

After the outbreak of the epidemic caused by EV-A71 in China, sequencing revealed that a mutation at an amino acid site (VP1-145) may be related to the increased neurovirulence and high pathogenicity of EV-A71, forming a new EV-A71 C4a subtype with VP1-145Q/G.

It is the mutation of "VP1 structural protein" that leads to increased severity of diseases caused by pathogens.

If it had been detected in advance, or even if vaccine development for the C4a subtype had been initiated in advance (it was later discovered that the current EV-A71 vaccine can cross-protect against other subtypes), then perhaps methods could have been found in advance to reduce the severity and death caused by the mutated virus, saving fewer children from the risk of sequelae and death.

I wrote a story about a baby who was infected with EV-A71 and developed severe hand, foot and mouth disease. He developed brainstem encephalitis and survived after receiving treatment, but had to rely on a ventilator to maintain his life due to respiratory paralysis (inability to breathe on his own). After insisting on treatment for 1 year, the parents were unable to continue supporting him and eventually chose to give up treatment. The child died due to inability to breathe on his own.

Of course, after the EV-A71 vaccine (commonly known as the "hand, foot and mouth vaccine") was approved for marketing, the number and proportion of severe hand, foot and mouth disease caused by EV-A71 in my country dropped rapidly (see figure below), and the number of deaths from hand, foot and mouth disease, a domestic notifiable infectious disease, was also gradually decreasing. Therefore, in general, with the EV-A71 vaccine, the risk of death from enterovirus infection in children has been greatly reduced.

Then through monitoring, it was found that the evolutionary distance between the CV-A6 sequences isolated after 2019 and the previously isolated sequences "has increased significantly". Just like the previous EV-A71, there may theoretically be a potential outbreak risk, so it is worth strengthening monitoring.

Continuous etiological monitoring is to better understand changes in the pathogen spectrum and to prepare for disease prevention in advance (including early warning, enhanced monitoring, drug development, intervention, etc.); as for the general public, "just take a look", the rest is to develop good hygiene habits and have children of appropriate age vaccinated with EV-A71 vaccine (after all, the decline in EV-A71-related severe hand, foot and mouth disease is closely related to EV-A71 vaccination. Recent studies have found that two doses of vaccination can protect against severe hand, foot and mouth disease caused by EV-A71 up to 100%).

In other words: EV71 vaccine is safe and effective, and still has high value in preventing severe hand, foot and mouth disease.

Finally, several companies have disclosed the development of multivalent vaccines covering CV-A6 (see figure below), but they are all in the preclinical stage, and currently only the monovalent EV-A71 vaccine is available.

willing

=Pill=

Disclaimer: This article was created out of personal interest, only to help more ordinary people have a clearer understanding of vaccines. The content and views do not represent any organization, unit, or institution, and it has not accepted any form of sponsorship. All pictures are from public online platforms. If the content is incorrect, please do more self-criticism (not).