Chongqing has its first imported case of monkeypox. Do we need to worry?

Yesterday, Chongqing City confirmed a case of monkeypox imported from abroad, becoming the first case of monkeypox imported from abroad in mainland my country. Fortunately, the case was isolated and controlled upon entering Chongqing, "with no social activities and low risk of epidemic transmission." The monkeypox outbreak in many countries around the world has finally come to China, which shows that epidemic prevention is not easy. Today, reviewing the scientific knowledge about monkeypox virus can help us adjust our mindset and calmly deal with this virus.

Written by Zhou Yebin (PhD, University of Alabama at Birmingham)

On May 29 this year, the World Health Organization issued a new statement on the Monkeypox virus, stating that as of May 26, a total of 257 confirmed cases of Monkeypox virus infection had been found in 23 countries around the world [1] . As of the time of writing, the latest data from the WHO showed that Monkeypox had spread to 30 countries [13] . On May 13, cases of Monkeypox virus infection in various countries began to be reported and summarized to the World Health Organization. From May 13 to May 21, only 92 confirmed cases of Monkeypox were reported [2]. Does such a significant increase in cases in a short period of time mean that Monkeypox will also pose a major threat to the world like the new coronavirus? With the constantly updated information related to Monkeypox infection, how much do we know about this virus now?

1 Monkeypox is not a new virus and has little to do with monkeys

Monkeypox is a relatively unfamiliar name to the general public. However, after more than two years of the COVID-19 pandemic, many people are highly nervous about new infectious diseases, and often worry that the next "COVID-19" will be a virus they have never heard of before. However, although monkeypox is an extremely unfamiliar name to most people, the monkeypox virus is not a newly emerged virus.

According to virus classification, monkeypox virus is a "close relative" of smallpox virus and cowpox virus, both of which belong to poxvirus. This virus was discovered in 1958, when a pox outbreak occurred in a group of monkeys raised for experimental research. Eventually, a new poxvirus was isolated and named monkeypox virus [3]. However, subsequent studies have shown that monkeys are not the main natural host of monkeypox virus. The main carriers of this virus are probably some rodents in Africa.

Not only is the monkeypox virus not a newly discovered virus, but cases of monkeypox infecting humans have also been documented. In 1970, the first human case of monkeypox infection was recorded in the Democratic Republic of Congo in West Africa[3] . Since then, cases of monkeypox infection have been frequently reported in Central and West Africa. For example, in 2017, Nigeria experienced an outbreak of monkeypox infection, with a total of 233 confirmed cases from September 4 to December 9 of that year [4].

Even outside of Africa, monkeypox infections have been recorded from time to time. From epidemiological studies, past cases of infection outside of Africa can be traced back to their African origins, such as infected people with a history of travel to Central Africa or West Africa.

An example of both the animal host characteristics of the monkeypox virus and the regional characteristics of the virus is the outbreak in the United States in 2003. At that time, a total of 47 suspected and confirmed cases of monkeypox were recorded in six states in the United States. To date, it is still the largest monkeypox outbreak in the United States. Through epidemiological investigations, all infections can be traced back to contact with pet woodchucks. However, this is not the case that woodchucks in the United States suddenly began to carry monkeypox virus. Further investigation showed that this batch of woodchucks sold as pets had been kept in the same warehouse as a batch of animals imported from Africa. The imported batch of about 800 small mammals, a total of 9 species, 6 of which were rodents. Subsequent testing found that 3 of the rodents were infected with monkeypox virus[5].

From this case, we can see that the main natural hosts of monkeypox virus are some African rodents, and direct or indirect contact with these animals is the source of human infection with monkeypox. It should be noted that since monkeypox virus has wild animals as natural hosts, our prevention against it is not aimed at completely eliminating the virus, but at limiting its spread to humans.

2 Is monkeypox infection dangerous?

During this outbreak of monkeypox, there were various descriptions of the dangers of this virus on the Internet, and some articles even threatened that the mortality rate of monkeypox could reach 10%, which is much more terrifying than the new coronavirus. In fact, this statement is very one-sided.

There are currently two branches of monkeypox virus, one is the Central African strain and the other is the West African strain. The data on the mortality rate of monkeypox infection are calculated based on historical records in Central and West Africa, where there have been more cases of infection. The mortality rate of the Central African strain is recorded to be about 10%, while the West African strain seems to be less threatening, with a mortality rate of 1% [6] . However, it should be noted that the mortality rate of any disease is affected by health and medical conditions. Monkeypox is even more special, and the mortality rate data mainly comes from areas with extremely limited medical conditions. It may not be of great reference value to many places. For example, in the two outbreaks mentioned above, in the United States in 2003 and Nigeria in 2017, there were no deaths, because the medical conditions in these two countries are better than those in Central and West Africa, where more deaths occurred.

As for the entire course of monkeypox infection, a lot of data has now been accumulated. The incubation period for most infected patients is 7-14 days, but it can range from 5-21 days. After the incubation period, the initial symptoms of infection include fever, headache, muscle aches, chills, fatigue, etc. [7].

Since monkeypox and smallpox are both poxviruses, monkeypox infection can also develop into pox disease. However, in terms of symptoms, monkeypox and smallpox are very different: monkeypox infected people will have swollen lymph nodes, which can be used as clinical evidence to quickly distinguish it from smallpox. Swollen lymph nodes actually prove that the human immune system is working hard to eliminate the viral infection, showing that the human immune system can effectively identify and attack the monkeypox virus.

Most patients develop a rash 1-3 days after the onset of fever, which is also a hallmark of poxvirus infection. The rash usually starts on the face and gradually spreads to the whole body. The rash eventually forms a scab and falls off, and the entire course of the disease lasts 2-4 weeks[7].

If compared to the more famous poxvirus, smallpox, which has a 30% mortality rate and is more contagious[8] , monkeypox transmission from animals to humans is primarily through contact with animals carrying the virus, especially through scratches or bites [7].

However, most of us do not have many opportunities to come into contact with African rodents, and many people are more concerned about human-to-human transmission. This type of transmission occurs during close contact. The body fluids and even the scabs of infected people are contagious. Most human-to-human transmission is caused by contact with infected people's pox, scabs, and body fluids. However, if there is close face-to-face contact for a long time, transmission through droplets and other routes is also possible [9].

It is not difficult to see from these transmission routes that monkeypox is transmitted based on close contact, and in most cases it is contact with the body fluids of infected people, which makes monkeypox less transmissible than the new coronavirus. The previous outbreaks since the 1970s also show that the transmission of this virus is relatively limited.

3 Why has monkeypox attracted widespread attention this time?

Since it is not a newly emerging pathogen, and we know a lot about its characteristics, from the course of the disease to its transmission ability, why has the attention on monkeypox continued to increase throughout May 2022?

This may be related to some "special characteristics" of this monkeypox infection outbreak.

First, the scope of monkeypox spread this time is beyond previous outbreaks. In the past, monkeypox infections were often confined to a certain country or region, but this time, in less than a month, outside of Africa, from Europe and the United States to the Middle East and even Oceania, 23 countries have reported cases of infection:

Table 1. Confirmed and suspected cases reported to WHO from non-monkeypox endemic areas between 13 and 26 May [1].

Since the monkeypox virus is not very contagious and due to the geographical distribution of its natural hosts, infections tend to be concentrated in parts of Africa. Therefore, it is more reasonable to assume that the virus only affected a certain country or a few countries due to travel history or animal trade. The sudden presence of infections in more than 20 countries may mean that the virus had been spreading for some time without being monitored by other countries . This is the main reason why the international community has become alert.

Secondly, there are many cases that do not have a direct travel history to Africa, which supports the "hidden" transmission in the past. Judging from the number of cases alone, 257 infections outside Africa are not many, and except for a few countries such as the United Kingdom, the number of cases in many countries is very small. However, unlike previous outbreaks, many confirmed cases in this country did not have a direct travel history to Africa. For example, the first case in the United States had a history of international travel, but it was to Canada, where it was infected [10]. This makes people more worried about whether monkeypox had been spreading outside Africa for some time before.

Furthermore, some cases in Europe and the United States are now transmitted from local human-to-human transmission, which undoubtedly increases the severity of this outbreak. Epidemiological surveys in the United Kingdom and elsewhere have shown that many cases occurred in homosexual men. The British public health department has also suggested that infected people should avoid intimate relationships during the infection period, and if they have intimate relationships for 8 weeks after recovery, protective measures are recommended [11].

Because of the spread within the same-sex community, some people have begun to speculate whether monkeypox is also a sexually transmitted disease, but there is no relevant evidence at present. For example, we do not know whether the monkeypox virus is present in the semen of infected people. The advice of the British Public Health Department is just a precautionary measure. These infections may be caused by physical contact with pox, scabs, etc. [9].

Although this monkeypox outbreak has the above worrying "unexpected" characteristics, a lot of information points to the fact that this is still the monkeypox virus that we know a lot about.

Sequencing results provided by several European countries indicate that the outbreak was caused by the West African strain, which has a lower mortality rate[1]. No deaths have been reported outside Africa, and most infections are not serious based on available information, which seems to be consistent with the West African strain’s lower pathogenicity.

In fact, given the severity of the outbreak, the situation in five African countries deserves closer attention[1]:

Table 2. Monkeypox epidemics in five African countries (Cameroon, Central African Republic, Democratic Republic of Congo, Nigeria, Republic of Congo)

The five African countries have reported more than 1,300 monkeypox infections, including 69 deaths. The Democratic Republic of the Congo, the worst-hit country, had 1,284 infections and 58 deaths as of early May.

So, we can see that Africa has been experiencing localized epidemics of monkeypox infection this year, which undoubtedly increases the risk of infection spreading to other parts of the world. And the infections seen outside Africa may be a manifestation of this risk of spread.

4 What tools do we have to combat monkeypox virus?

Recently, some articles on the Internet have expressed extreme concern that monkeypox has no cure, which is also a very one-sided statement.

There is currently no proven treatment for monkeypox, but this does not mean that we are helpless against monkeypox.

First, most monkeypox infections are relatively mild and not life-threatening. Therefore, most infected people only need some maintenance treatment and do not need to panic because there is no specific medicine.

Secondly, because it is similar to the smallpox virus, the smallpox vaccine also has a certain degree of protection against the monkeypox virus. According to historical data from Africa and other places, the effectiveness of smallpox vaccination against monkeypox is about 85% [1]. However, as smallpox has been eradicated, most parts of the world have long stopped large-scale smallpox vaccination. Therefore, the immune protection of the population against monkeypox is relatively weak. However, the use of smallpox vaccines in key populations can still help us deal with this monkeypox outbreak.

The relatively long incubation period of monkeypox virus means that smallpox vaccination may have a role in post-exposure prophylaxis even after exposure. For high-risk contacts, such as family members of infected people and medical staff, smallpox vaccination can be considered as soon as possible after exposure to the patient. According to previous studies, vaccination within 4 days of exposure may have a better effect [1].

In terms of antiviral drugs, tecovirimat has been approved by some countries for the treatment of monkeypox virus. However, due to the limited monkeypox epidemics in the past, this type of antiviral drug is more based on evidence from animal experiments, and there are some cases of compassionate use, so the clinical effectiveness is not sufficient.

For example, on May 24 this year, British researchers published a paper in The Lancet, which reviewed and analyzed seven cases of monkeypox infection in the country from 2018 to 2021 [12]. One of the infected people was treated with tecoviridavir, and both the viral load and clinical symptoms improved after taking the medicine. However, such individual cases are obviously not enough to prove the effectiveness of the drug. However, if the monkeypox epidemic spreads further, or patients begin to develop more serious symptoms, then this type of antiviral drug will still be an option, at least as a compassionate use drug.

In addition to these vaccines and drugs, we should not forget the usefulness of epidemiological research-based methods such as isolating infected people and reducing the risk of close contact. From the results of genome sequencing, the monkeypox virus in this outbreak is not much different from previous outbreaks [1]. Combined with the current case tracking, monkeypox is still a disease that is not very contagious and requires close contact to be transmitted. Closer screening of people with suspected pox symptoms and timely blocking of transmission will be a very important response measure and is very likely to be effective.

Of course, having these response tools doesn't mean the current monkeypox outbreak isn't a challenge.

On the one hand, the actual number of infections in many countries may be much higher than what is currently counted. In the monkeypox epidemic update on May 29, the WHO summarized the total number of cases as of May 26 as 257, but at that time many countries still had many suspected cases under analysis. On May 31, the head of the WHO Monkeypox Technical Working Group said in an interview that the number of cases had risen to 550, affecting 30 countries[13]. As of June 2, the number of cases had risen to 643[14]. This undoubtedly means that the spread of the virus is more serious than before, and more countries and regions need to participate in prevention and control.

On the other hand, the global stockpile of both smallpox vaccines and potential drugs such as tecovirida is limited [1]. At this stage, except for a few high-risk groups, most people will not need to get a smallpox booster shot or take antiviral drugs. However, the monkeypox virus has spread to so many countries that it will be a challenge to allocate the stockpiled drugs to achieve the greatest effect and expand the reserves in a timely manner.

However, we do not need to panic about the current monkeypox epidemic. The threat facing humanity is that if it is not controlled in time, the monkeypox virus will spread further. If a relatively stable population is infected, we will be in danger of having to deal with this virus for a long time. The WHO and public health organizations of various countries are constantly updating information and improving response plans, not to make people panic and worry that monkeypox is the next COVID-19, but to control the spread of the virus as soon as possible by strengthening the screening of suspected cases.

In terms of infectiousness, spread, and overall number of cases, monkeypox cannot be compared with COVID-19. However, both have an initial invasion route from wild animals to humans. With the development of human society, our "conflict" with nature has also intensified, including the continuous "invasion" of our lives by various viruses whose natural hosts are wild animals. How to deal with this long-term threat of new infectious diseases may be a question that the public health field needs to think about continuously in the future.

References

[1] https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON388

[2] https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385

[3] https://www.cdc.gov/poxvirus/monkeypox/about.html

[4] https://africacdc.org/disease/monkeypox/

[5] https://www.cdc.gov/poxvirus/monkeypox/outbreak/us-outbreaks.html

[6] https://www.gov.uk/government/publications/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement/principles-for-monkey pox-control-in-the-uk-4-nations-consensus-statement#:~:text=There%20are%202%20clades%20of,occasionally%20exported%20to%20other%20regions.

[7] https://www.cdc.gov/poxvirus/monkeypox/symptoms.html

[8] https://www.fda.gov/vaccines-blood-biologics/vaccines/smallpox

[9] https://www.cdc.gov/poxvirus/monkeypox/transmission.html

[10] https://www.cnbc.com/2022/05/20/what-is-monkeypox-and-how-dangerous-is-it-cases-are-rising-globally.html

[11] https://www.gov.uk/government/news/public-health-agencies-issue-monkeypox-guidance-to-control-transmission

[12] https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00228-6/fulltext

[13] https://www.cnn.com/2022/05/31/health/monkeypox-update-who/index.html

[14] https://www.cnn.com/2022/06/02/health/monkeypox-endemic-silent-spread/index.html

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