Gustavo Palacios: "We don't know if monkeypox is being transmitted explosively"

Gustavo Palacios (Buenos Aires, 1969) is a virologist at the Icahn School of Medicine at Mount Sinai (New York, United States) who studies emerging pathogens and their transmission. Some are as well known as Ebola, while others are ignored by the general public until they start making headlines. The latest example is monkeypox, which has risen to prominence in recent weeks.

In 2018, Palacios delved into the genome of the monkeypox virus responsible for an outbreak in Nigeria that began the year before, is still not over, and continues to export cases around the world. We speak with him during one of his brief respites to better understand what is going on and, once again, to ask something that virologists and epidemiologists have grown tired of hearing in recent years: how much longer?

Why did you decide to study monkeypox?

Because there are hypotheses that suggest that the ecological niche occupied by smallpox may be occupied by another pathogen of that family. It is not understood, if we want to avoid this risk, why we do not ensure the eradication of monkeypox in the affected human population in the Congo and West Africa for more than 30 years. It is surely a small cost now that we know what we can do about infectious diseases. If we boast of making a vaccine in a year, how can we not solve this problem?

Is the origin of this outbreak in Europe known?

We don't know, but most likely a new introduction from West Africa. The health system should be global and think about whether it would not be convenient to pay so that the populations that are in contact with rodents [que act├║an de vectores] have better health coverage. Convince people by the pocket and say that if you put money in those areas you can avoid having problems in others.

You have studied the disease in Africa, but do we know how the virus is going to behave in a Western city?

What we know so far is how it has behaved in the past and we know that in first world systems infections by close contact are much lower due to the availability of water and hygiene. There is much less hepatitis in the first world than in developing countries, for example. It is illogical to think that it will behave in another way in which it will be more transmissible. No, it will be less, that without a doubt. And it is not because we are better but because there are more resources.

Is it spreading explosively or are we just now seeing all the hit cases?

I don't want to use that term "explosive" because we don't know. We know that it is transmitted by close, physical contact, through biological fluids, one of which is the vesicles, in which there is a high concentration of the virus. All human activities that generate that contact will facilitate transmission. I don't want to use the word intimate because of how it sounds, because it doesn't necessarily have to be sexual. Close contact maybe, but that sounds like COVID-19 and there has to be physical contact here. You have to touch those biological fluids for transmission to occur. In the 2003 outbreak it was due to the importation of a rodent. In this case we can't even say that. We don't know if there are any rodents involved or if it's all human-to-human transmission.

Cases outside of Africa had always been fairly isolated. What has changed?

We are working to understand if there is something different in this situation compared to previous ones. There are environmental changes: we have a majority of the population that has not been exposed or, in the case of those under 45, vaccinated. This generates an increase in susceptible organisms, which may be one of the reasons behind the change. Over time we will see if that is what happened, but to find out it is necessary to carry out more extensive studies.

Another issue is epidemiological. Where did the virus come from? It may be an import from endemic areas, as we have seen so far; or not, and that the virus already resides in Europe and other Western areas. A circulating hypothesis is that it has been transmitted to rodents in those areas.

A third possibility is that the virus has changed. Seeing what we can learn from the viral genome is the first and easiest thing we can do. We know that viruses are closely related, that it is probably all due to a single introduction, and that it is the clade circulating in West Africa. It has a lower virulence rate and should be less transmissible between people.

Do these data already allow us to know if the virus has changed to become more transmissible or are they too preliminary?

There is a problem and that is that we want to know everything now. We have a 200,000 base pair DNA virus. [200 kilobases] sequenced less than a week after the first case of concern was reported. The first sequence had some uncertainty, but allowed us to conclude that it was the West African clade and that there were very few changes. Now it is even more perfect and we are more confident that there are few changes.

So you don't think what we're seeing is because the virus has become more contagious.

The only thing I can say is that when we compare with the last introduction [de 2018] there are 20 different amino acids, in many different proteins, relative to the last thing we know. But we also don't know what the last thing we know is, or how transmissible that virus was. All we know is that this outbreak started and ended quickly. Perhaps because there was no supercontagious event where it spread more, but we do not know if this virus is more transmissible or not than the one in 2018.

We are talking about a genome of 200,000 base pairs with hundreds of proteins, many of which we do not know what they do, we have not detected and we do not know if they are real. Some changes are based on proteins that we predict exist but have not seen. It remains to be seen how many of those 20 changes are in proteins that are important for virus replication.

Of all the hypothetical proteins that the virus has, the one with the most changes has two amino acids. It is very difficult to think that what we are seeing is due to a couple of changes in some proteins. I would tend to think that this has nothing to do with it, that there is some other change, environmental or transmission.

How long do you think the virus has been circulating in countries like Spain?

The answer to that question has to do with how little we know about the disease. How alone we leave countries that have these problems when we don't have them in the first world. I worked in the Congo with cases of monkeypox and we characterized the samples that came to us. They tell you most have rashes and blisters and you think most have symptoms. You do not think that there are cases that do not go to the health system because they are going to leave them waiting with hundreds of people for hours and in the end there are no resources to treat them. Many do not go, they prefer to stay at home and that is why we only see severe cases.

Then we want to take back what we learned in a low-resource context and transfer it here and say how come so many cases escaped us. Who knows, maybe they didn't escape, maybe it's normal and we just always see the most serious cases and not the mildest, but we tell doctors to be aware of those more striking pictures.

Don't you think it's difficult for a disease like this to have gone unnoticed for a long time in countries like Spain?

Yesterday I was put in front of a bunch of photos of arms full of pustules during a meeting. A doctor who is not an infectious disease specialist, if he does not see this picture, perhaps he does not think of monkeypox. The same with our health system. I don't know if it's weird or not that it wasn't seen until the alarm went off. In almost all countries, the microbiological laboratory receives the samples based on what the doctor sees and reports. It is very likely that in Spain and other places they only began to think about this, which is never seen in Europe, when they saw it in the United Kingdom and alerted them. From there they began to ask for the studies and they found it.

So, do you think the detection systems have failed?

I don't think there are any flaws because I don't think the system we've built around the world is that good. You cannot think that a system fails if you did not build it for that. I have worked all my life in virology, clinical diagnosis, in the discovery of pathogens and their transmission, and until recently you went to the doctor and he told you that it was viral and that you should stay at home for a week. The system wasn't trying to figure out which respiratory virus was causing your infection. And it still doesn't. Then nothing failed: you have what you have. If you want something better, invest more money.

I mentioned earlier the rodent hypothesis, which is something that ECDC is concerned about. Do you think there is a risk that the virus will jump to these populations or even that it has already done so?

There is nothing to indicate this, but if we were to find rodents in the rest of the world with the virus, that would generate a different situation, with a different risk for the health system. If there were a surveillance system that was looking at rodents in the United Kingdom or the Canary Islands, it could tell you that it does not circulate in animals in the area, but we do not know because there is no support to do so or to look for it in the endemic area.

We know a lot about the cases that happen in the West, but there are many in endemic areas that we are not characterizing due to a question of resources and how their health system is. Now we are very impressed by a disease of which there are thousands of cases every year in Africa. Cases that we do not study. In reality, we do not know what is circulating; nor in the rodent population, both in Europe and in endemic areas. That is very important for many of the debates, but it is very difficult to answer the question of where it comes from, because we do not know what is around us.

What should we do now?

The most important thing now is to try to do contact tracing. See where it came from and what is the index case. Because the only thing we know is that a few weeks ago in the United Kingdom they identified some cases, but these do not have to be the first. The WHO asks to study all cases since March 15 with these symptoms in case we find more that were not diagnosed because they thought it was chickenpox or something like that. By studying those samples we may be able to identify the initial cases, see if they traveled to Africa, and piece together the story.

How much should we worry?

From a pandemic standpoint, I don't think the general population has anything to worry about. It is absolutely controllable. The classic ways of separation and avoiding contact are enough to stop it. In addition, we have vaccines and antivirals. The smallpox vaccine has 70% protection and you can do a ring vaccination to immunize all contacts and stop transmission.

From the epidemiological and environmental point of view, it opens up a series of questions depending on where this new risk is, which until recently was only in the traveller. If the conclusion of these investigations is that monkeypox has become established in the rodent population in other areas of the world, that would change the equation and it would be necessary to see what to do.

After this initial scare and with the measures applied, do you think these outbreaks will die out?

I would hope so. All countries and health systems have received the alert and are searching. People also listen to the media and if they have a swollen tonsil or a small lump or gallbladder they will probably go to the doctor and avoid contact.

Is it time to open the debate about vaccinating the rest of the population against smallpox?

When smallpox was eradicated and it was decided to stop vaccinating, we had a population that was very receptive to vaccination. The criteria was: there is no problem in stopping vaccinating because it is not circulating, and if necessary we can vaccinate very quickly. But if we have learned anything in recent years, it is that there is resistance to vaccination, and I don't know how effective those plans would be. You can't force people to get vaccinated because you generate more resistance, but you have to design a health system that doesn't count on the majority of the population being vaccinated.

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