Monkeypox: a new killer virus?

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On April 29, a Briton visiting Nigeria noticed a strange rash on his body. On May 3, he returned to Great Britain, went to a doctor, who immediately sent the traveler into isolation, suspecting he had monkeypox. On May 7, the diagnosis was confirmed, and the doctors immediately notified the WHO. All those who had been in contact with the infected person were placed under a 21-day quarantine, and on May 16, the WHO reported there was no danger of spreading the virus. But two days after reports came of a second case of monkeypox recorded in England on May 13: the first patient's partner who was living with him in the same house became ill. On May 15, a few more laboratories confirmed four new cases, all in homosexual men who had visited sexual health clinics. None of them had traveled to Africa in the recent past, where many countries are endemic for the monkeypox virus.

Over the following days, dozens of cases were identified, and not only in England: by the end of May, monkeypox cases had been confirmed in 12 countries, not only on the European continent, but also in the United States and Canada.

The disease

Monkeypox is caused by a poxvirus, not unlike smallpox and cowpox viruses (varicella virus, despite its name, belongs to a completely different group of pathogens). Monkeypox is not a new disease. The virus was discovered in 1958 in the monkeys kept in the vivarium of a Danish laboratory, hence the name. However, monkeys are not the main natural reservoir of the virus: it can infect them, but the pathogen's favorite hosts are various African rodents. In 1970, the virus for the first time infected a human, a 9-month-old boy from the Democratic Republic of Congo. Soon his father also became ill. How they contracted the virus is not entirely clear, but it is known that the family liked to eat monkey meat.

Since then, cases of monkeypox virus infection have rarely but regularly occurred in Congo and the neighboring countries. Symptoms of the disease resemble those of smallpox, but the course is milder. At the end of the asymptomatic incubation period, patients develop fever, swollen lymph nodes, headaches, and muscle pains. After a few days, the characteristic rash appears on the body, and soon turns into fluid-filled papules. Gradually papules dry out and become covered with crusts, which eventually fall off. On average, the disease lasts 2 to 4 weeks. Infection occurs through close contact when body fluids of a patient, especially the fluid from papules, gets on the skin or mucous membranes of another person. In addition, infection is possible via fomites, i.e. objects which have also come into contact with biological fluids containing the virus. The lethality of monkeypox ranges from 3% for the West African strain to 11% for the strain common in Central Africa.

In 2003, monkeypox developed in humans outside the African continent. The outbreak occurred in the United States, in the state of Texas, where 47 people were infected by meadow dogs, rodents often purchased as pets. The meadow dogs were American, but the seller kept them in the same room with rodents imported from Ghana. The infected African animals transmitted the pathogen to the dogs. Since then, the virus has been detected in humans in Israel, Singapore, the United States, and the United Kingdom, but all those who became ill had traveled to Africa shortly before the symptoms appeared. There has been no independent spread of the infection throughout the population with no obvious link to countries endemic for the virus.

New unusual outbreak

The current outbreak differs noticeably from previous outbreaks precisely because nobody but patient number one traveled to Africa and did not seem to have been in contact with those who had recently returned from there. Moreover, the vast majority of the initial patients were homosexuals. This unusual pattern has led some specialists to speculate that perhaps the virus has changed and acquired the ability to be transmitted sexually.

However, as data on the contacts of those infected became available, another hypothesis gained prominence: many of those who showed symptoms of the disease had attended LGBT parties in Belgium and Spain, including the big Gay Pride festival in the Canary Islands. At such events, many people get in close contact with each other, and if one or more of them are infected, they can infect many people within a short period of time. That is, transmission through semen or vaginal secretions is not required, just close bodily interaction, which is abundant at parties - and it does not matter at all whether the contacts identify themselves as homosexual or heterosexual.

Such mass infection events are called superspreading, and they are largely responsible for the covid epidemic in Europe, when snowboarders and ski enthusiasts from various European cities contracted the coronavirus at a resort in Tyrol in late February or early March 2020.

Within days of the outbreak, researchers presented the first sequences of the virus genome. The pathogens detected in the Belgians, Portuguese and Germans most likely originate from the same source (another indirect confirmation of a superspreading event), and they are very similar to the virus that was imported from Nigeria to the UK, Singapore and Israel in 2018-2019.

This virus belongs to the less pathogenic West African species. However, compared to the genomes from two and three years ago, the viruses that are spreading now carry several dozen point mutations. That's quite a lot, especially considering that the monkeypox virus is a double-stranded DNA-containing virus, and it usually evolves quite slowly. More definite conclusions about how and why the virus has changed so noticeably can be drawn after scientists have sequenced more genomes.

Why now?

The number of monkeypox cases has been steadily increasing. In the 1970s, 47 cases were reported, but by the 1990s the number had risen to 520. While more than 10,000 infected people were registered in the Democratic Republic of Congo from 2000 to 2009, there were more than 18,000 in the following decade. In 2020, there were 6,257 confirmed and possible cases in Congo.

Scientists attribute this dynamic to a decline in population immunity against smallpox. The smallpox viruses that cause smallpox and monkeypox are similar, and a fresh smallpox vaccination provides 85 percent protection against the monkeypox virus - as does the immunity remaining after the disease. After 1980, children stopped being inoculated with smallpox vaccine, and the number of monkeypox cases started to increase with each year. Initially almost all those who fell or died from the disease were children under 10 years of age who had no immune protection against poxviruses. Over time, older people became infected and died, and now the average age of death is 27 years (although children under 10 still account for 37.5% of all deaths).

Today, all people born after the mid-1980s have no antibodies or cellular immunity against poxviruses. In the absence of the smallpox virus, which was very effective in infecting humans, its niche has been taken by the monkeypox virus, which is less active in terms of infection, but not much less. Moreover, while humans were the only host for the smallpox virus, the monkeypox virus can constantly jump to humans from animals.

Vaccinations and medications

Unlike the coronavirus, against which there was neither a specific cure nor a vaccine at the beginning of the pandemic, there are effective ways to deal with monkeypox infection and its aftermath. First, humanity still has a live vaccine, i.e. a vaccine based on a virus similar to the one that causes smallpox, the vaccine which completely eradicated the virus by 1980 in the course of the worldwide anti-smallpox campaign. Moreover, after the terrorist attacks of 2001 and 2003, governments around the world (especially in the U.S.) were concerned with setting up preventive measures against possible use of biological weapons.

As part of this program, an anti-smallpox vaccine was developed containing a modified virus from the poxvirus group that could not reproduce. The virus based on that vaccine can infect the cells of a vaccinated individual but cannot synthesize new viral particles. Such vaccines are usually more easily tolerated, and there's no risk of the virus accidentally becoming fully active and developing disease. Both vaccines are effective in combating the virus that causes monkeypox and in post-exposure prevention, that is, in the first days after the person has had contact with the disease.

In addition, scientists have created several antiviral drugs that prevent the smallpox virus - and, as animal studies show, the monkeypox virus - from infecting cells. Two of them have already been approved by U.S. and European regulators for use in humans (only one of them, tecovirimat, has been approved in Europe). In the U.S., 1.7 million doses of tecovirimat are already in storage as a strategic stockpile; European countries and Canada are in talks with the manufacturer to purchase the drug in the near future.

A new pandemic?

Unlike the coronavirus, the monkeypox virus does not spread via airborne or aerosol transmission. To become infected, you need to get in close contact with a sick person or his or her belongings. Therefore, even though there has been a gradual increase in infections since the 1970s, the total number of cases so far has not exceeded two thousand per year. In other words, monkeypox is still a very rare disease.

Nevertheless, because of humans' global lack of immunity to poxviruses and the existence of a permanent natural reservoir, i.e. monkeys, the pathogen is able to enter and spread throughout the human population at any time. If such «forays» become regular and the virus reproduces frequently in humans and is transmitted from person to person, it could mutate in such a way as to facilitate infection. The return of universal anti-vaccination could prevent such a scenario.

Although there is no natural protection against human infection right now, there are ways to stop the spread of the virus and reduce the risk of severe consequences. In the U.S. and several European countries where monkeypox has been identified, so-called ring vaccination has already been initiated, where doctors administer the smallpox vaccine to anyone who has come in contact with an infected person. For diseases with a long incubation period, including monkeypox, post-exposure vaccination makes sense because the immune system manages to trigger the production of antibodies to combat the pathogen. For those who do get sick, there are two antiviral drugs that have shown good efficacy in animal experiments.

In most healthy adults, however, the likelihood of severe or fatal complications from the monkeypox virus infection is low - although numerous scars may remain on the body after the papules have healed. The risk group includes young children, the elderly, and people with weakened immune systems. However, most elderly people should retain partial immunity after smallpox vaccination.

To what extent it persists many decades after the vaccination is difficult to say: studies of the antiviral activity of antibodies in those vaccinated during the anti-smallpox campaign yield mixed results. In some people, antibodies recognize the virus well and can disable it, but in a lot of cases it doesn't happen. However, antibodies account for only some of the protective mechanisms: there is also a cellular component of immunity, which is more difficult to test in the laboratory and which can protect a person from a severe course even if he or she gets infected.

Thus, most experts remain relatively calm for now. Unless the monkeypox virus has acquired enough genetic changes, for example, to learn to spread asymptomatically or to become more contagious and transmittable other than via close contact, humanity will probably be able to quell the outbreak. But globally, the spread of the virus remains an open issue, and given that it can only be solved by vaccination, the success of such a project is doubtful.

The covid pandemic has shown that repeating the success of the anti-smallpox campaign and vaccinating the majority of the world's population without the use of emergency measures is impossible today. Experts have no clear ideas on how to overcome people's reluctance to be vaccinated, even against very dangerous pathogens.