With the release of a new round of monkeypox virus gene sequencing reports by research teams in many European countries, including France, Italy, and Spain, more and more evidence shows that monkeypox has occurred in large-scale community transmission in Europe.

  With so far known cases of monkeypox mainly among men who have sex with men, global health officials are reminding the community to be on high alert for monkeypox symptoms as June approaches.

  Monkeypox, a zoonotic disease caused by monkeypox virus (MPXV), is considered the most important orthopoxvirus infectious disease in humans since the eradication of smallpox.

Monkeypox virus can be transmitted from person to person through diseased organisms, body fluids, respiratory droplets, and pollutants, but human-to-human transmission usually requires prolonged close contact.

The fatality rate of monkeypox is about 1%-10%, with the highest death rate in children.

Before the current outbreak, monkeypox cases were mainly scattered in the tropical rainforests of central and western Africa, and cases outside Africa were thought to be related to African travel.

  This round of monkeypox epidemic is spreading rapidly around the world, and the transmission path is unusual, which is really rare.

The World Health Organization has confirmed that more than 300 confirmed and suspected cases of monkeypox have been detected in about 20 countries around the world since the first case of monkeypox was detected in the UK in early May.

Most of the cases are men who have had sex between men.

Some analysts believe that the large-scale sexual behavior in the previous two carnival parties in Europe may be the main reason for the spread of monkeypox in this round.

  In Europe, scientists are still intensely sequencing the genome of the latest monkeypox virus.

This provides a clearer resolution for tracking the spread of the virus in the current outbreak.

  As of the time of writing this article, the latest nine monkeypox virus gene sequencing reports from France, Italy, Spain, the Netherlands, and Belgium have been published one after another. The relationship between the clades and virus samples is extremely close, further confirming that large-scale community transmission of monkeypox has occurred in Europe.

  Previously, João Paulo Gomes of the Portuguese National Institute of Health and his colleagues had published 10 genome sequencing reports of monkeypox virus carried by Portuguese monkeypox patients, and analyzed that the current round of monkeypox epidemic The outbreak is most likely from one source.

  On May 27, local time, the Italian research team released the first genome sequencing report of the virus samples from Italian monkeypox patients.

The 33-year-old man arrived in Italy from Portugal on May 18. He visited a local hospital for perianal ulcers, bilateral inguinal lymphadenopathy, a small amount of papular and vesicular skin lesions on both elbows, back, buttocks and left foot. For several days, the patient had a fever (38.5°C) for one day, accompanied by sore throat and sneezing.

The research team used the Illumina platform to sequence the genome of the virus sample carried by the case, with a sequencing depth of 19 times.

The analysis results showed that the monkeypox virus genome carried by the patient belonged to the West African clade and was closely related to the genome sample uploaded by the Portuguese team.

  On the same day, the Spanish team published the first genome sequencing report of a monkeypox virus sample in Spain.

The coverage of the draft genome was 98.6%, and the average sequencing depth was 77 times.

The virus genome belongs to the West African clade of monkeypox virus. Compared with the most closely related Portuguese branch sequence, the single nucleotide diversity loci (SNPs) are less than 4. Compared with the German sequence, the single nucleotide diversity There are 2 sites (SNPs).

  The Dutch research team published the first report on the genome sequence of a Dutch monkeypox virus sample the day before. The team used the Nanopore gene sequencing platform with a sequencing depth of 10 times.

The researchers said in the report that the virus is very similar to the genome sample published by the Portuguese team in the evolutionary tree. Compared with the most closely related Portuguese sample, only 2 single nucleotide diversity loci (SNP) appeared. s).

  In addition, the first viral genome sequence from France and the second viral genome sequence from Belgium both showed extremely high similarity to the first published gene sequence in Portugal, and all belonged to the West African branch on the viral gene evolutionary tree.

  The Italian research team further stated that "the current genome sequencing results further support the conclusion that large-scale community transmission of monkeypox virus has occurred in Europe."

  In addition, it is still worthy of high attention that on the evening of May 28, Beijing time, the French research team released the latest full sequence sequencing report of the monkeypox virus carried by a French patient. Four gene samples passed the Illumina sequencing platform, and the sequencing depth reached 950 times - this is also the deepest sequencing to date (the deeper the sequencing depth, the more accurate the measurement).

The results showed that, compared with the monkeypox virus gene found in the UK in 2018, 46 single nucleotide polymorphism sites (SNPs) and 3 deletions appeared in these four virus gene samples.

  Previously, Andrew Rambaut, an evolutionary biologist at the University of Edinburgh, said: "We estimated that the genome of variola virus (a relative of monkeypox, also belonging to the genus Orthopoxvirus) has about 1x10 per locus per year. -5 substitutions, resulting in an average of 1-2 nucleotide changes per year in the virus. This is the high end of the estimate." The researchers said that the nucleotide mutation rate of monkeypox virus is obviously beyond people's expectations.

  Global health officials urge sexual minorities to be on high alert

  According to the Italian research team, based on the information currently available, most of the known monkeypox cases occur mainly but not exclusively in men who have sex with men, and the confirmed symptoms are perianal, genital lesions, and a few skin lesions have a synchronous evolutionary pattern.

  And June is coming next week.

Every June is the "pride month" for sexual minorities (gay, bisexual, genderless, transgender, etc.) around the world, and there are usually a series of parades around the world.

Against this backdrop, health officials around the world are working to raise awareness of the spreading monkeypox outbreak.

  At the same time, they are also trying to strike a delicate balance of spreading the warning message that monkeypox may currently pose a risk to MSM, but not associating this group with a group that can infect anyone under a given condition virus, thereby stigmatizing this group.

  Demetre Daskalakis, director of the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention, said, “In reality, our message to all communities is similar, and if there is a A normal rash, then maybe monkeypox, be vigilant," Daskalakis said. "If a rash develops after next month's event, it's important to see a doctor, knowing that the virus may be in some societies. spread in groups."

  In previous cases, monkeypox is not considered a sexually transmitted disease like AIDS, and so far there is no evidence that monkeypox virus is transmitted through semen or vaginal secretions.

During this outbreak, there have been multiple reports of genital or penile damage in infected individuals.

Therefore, if one partner is infected, close contact between people during sex may lead to transmission.

  According to Anne Rimoin, a professor of infectious disease epidemiology at the University of California, Los Angeles, the outbreak is "worrying" rather than "scare".

She said it remains to be seen how severe the disease could be if monkeypox virus spreads among HIV-infected people.

But she stressed that the current situation deserves attention.

  "We just wanted to keep a close eye on it and understand the series of chains of transmission that could arise in these populations," said Limoyne, who has been studying monkeypox viruses for more than 20 years. "The monkeypox virus is spread through close contact, and sexual contact is by its very nature. It's close contact. It has nothing to do with gender or sexual orientation. It can infect anyone with similar close contact."

  Still, some experts are concerned that the disease could lead to more severe disease in HIV-positive and immunocompromised people.

  Chikwe Ihekweazu, former head of the Nigeria Center for Disease Control, said: "In its own case, monkeypox is usually a self-limiting viral infection that causes unpleasant skin damage. But most people recover on their own. But Now, we have to think about the effects on patients of this virus binding to other viruses like HIV."

  In 2020, Ihekweazu published a paper in the internationally renowned journal "Clinical Infectious Diseases", saying that HIV-infected people infected with monkeypox in Nigeria between 2017 and 2018 were more severely ill than those infected with ordinary monkeypox.

According to the US scientific website www.statnews.com, Spanish health authorities revealed that the two earliest cases of monkeypox in Spain were HIV-infected people.

  And David Heymann, chair of the World Health Organization's expert committee on health emergencies, said, "We now have to accept the fact that in some high-risk groups the monkeypox virus has taken hold," he said. , "I think it's true that the virus has spread widely. But I'm not quite sure what will happen in the long run."

  Daskalakis said that the US Centers for Disease and Prevention is currently disseminating warning information through various channels such as social media, medical services and social applications.

  To stop monkeypox virus from becoming a human pathogen, aggressive detection of cases to break the chain of transmission will be critical.

"People would be concerned that the virus would become more adapted to humans. The chance that monkeypox would find the perfect solution to get out of Africa was very small, but it did," Limoyne said. "We can see that every other After a while, there will be a virus that will be a big hit."

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