This article was written by Wang Preli
July 23 , WHO declared monkeypox a global public health emergency of international concern,
Screenshot of WHO’s official website
WHO Director-General Tedros Adhanom Ghebreyesus said in a statement that, according to the International Health Regulations, is deciding on a certain The Director-General should consider the following five elements when whether an event constitutes a public health emergency of international concern:
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First of all, the information provided by countries now shows that monkeypox has spread rapidly to many countries where monkeypox has never been seen before; span>
Secondly, according to the International Health Regulations, the standard for declaring a public health emergency of international concern has been reached;< /span>
Thirdly, the opinion of the Emergency Committee has not yet reached a consensus;
Fourth, scientific principles, evidence and other relevant information are not sufficient at present, and there are still many unknowns;
Fifth, risk to human health, international spread, and potential for interference with international traffic. Currently, WHO estimates that the risk of monkeypox is High in Europe and medium in the rest of the world. According to Tedros, more than 16,000 cases of monkeypox have been reported in 75 countries and territories around the world, including 5 deaths.
A smallpox-like virus
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On May 7, 2022, the UK first reported a confirmed case of monkeypox who had returned from a trip to Nigeria. Subsequently, several countries have reported monkeypox cases, spanning Europe, North America and Africa.
Monkeypox virus, first reported in 1958 in Copenhagen, Denmark, in cynomolgus monkeys infected with vesicular disease from a polio vaccine study The virus was isolated from. In the following ten years, monkeypox only spread among animals, and no human infection with monkeypox virus was found.[1].
By 1970, I.D. Ladnyj, then WHO VARV Eradication Program Officer, was in the Republic of Congofrom Monkeypox virus was isolated from a 9-month-old infant suspected of being infected with smallpox virus, which is also the first report of monkeypox infection in humans[2].
The baby was born in a large family, except for him, other family members were vaccinated against smallpox virus, and the patient was in After suspected exposure to the monkey meat for consumption, clinical manifestations similar to smallpox appeared, such as fever and body rash.
But strangely, after the rash subsided, the baby had otitis, mastoid inflammation and lymphadenitis, which did not correspond to the clinical manifestations of variola virus infection, and thus attracted the attention of I.D. Ladnyj.
A series of laboratory tests later confirmed that the baby was the first human case of monkeypox virus infection. Since then, the World Health Organization has classified monkeypox virus infection as a viral zoonotic disease.
In the 50 years since the first monkeypox infection was identified, monkeypox virus has spread in 15 different countries around the world. Sporadic or localized outbreaks are mainly concentrated in 11 countries in Central and West Africa. There are only sporadic cases reported in Europe and North America, all related to imported cases.
As a DNA virus, the monkeypox genome is a double-stranded DNA strand with closed ends [3]. After contacting with the host cell, it enters the cell by “fusion” or “endocytosis”, followed by viral DNA replication and viral protein assembly in the cytoplasm, and finally in the Golgi or endoplasmic reticulum “envelope”. It is released from the cell by “exocytosis” or directly after lysing the cell.
Most of the clinical symptoms of monkeypox virus infection in humans are similar to those of smallpox virus infection, but the symptoms are milder.
The prodromal symptoms are fever, headache, and generalized fatigue. Lymphadenopathy (1 to 4 cm in diameter) in the maxillary, neck, or groin region, with lymphadenopathy and tenderness, is most strikingly different from variola virus infection in many patients before the characteristic rash. indicates that monkeypox virus may activate more effective immune recognition and response than variola virus[4].
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The rash first appeared on the face, and then rapidly developed to the whole body, showing a centrifugal distribution. The number of rashes varies from a few to thousands depending on individual differences. etc., generally go through the macular stage, papule stage, herpes stage and pustular stage until the scab falls off. During this period, nearly 19% of unvaccinated individuals may be combined with skin bacterial infection and aggravate the disease.
Severe complications and sequelae were more common in unvaccinated patients (74% vs 39.5%) [5], including secondary pulmonary infection, vomiting and diarrhea, etc. A very small number of patients can be combined with encephalitis and eye infection resulting in permanent vision loss.
Monkeypox virus infection in patients with cervical lymphadenopathySource: Reference
Lancet latest: 2 drugs likely to work
On May 24, 2022, a retrospective study from the United Kingdom was published in the Lancet journal Lancet Infectious Diseases.
Image source: Paper screenshot >
Hugh Adler and his team of researchers analyzed the clinical characteristics of monkeypox patients diagnosed in the UK between 2018 and 2021, including virological characteristics and response to antiviral drugs. A total of 7 patients were included in the study, 3 women and 4 men.
The results showed that the clinical features of monkeypox were: viremia, prolonged nucleic acid detection time in upper respiratory tract swabs, reactive emotions In addition, one patient developed nucleic acid positivity in a deep tissue abscess. Due to the long period of nucleic acid positive, 5 patients were quarantined for more than 3 weeks.
The study also compared the efficacy of the anti-variola virus drugs Tembexa (Brincidofovir) and Tecovirimat in the treatment of patients with monkeypox infection. safety.
Tembexa is a nucleotide analog lipid conjugate and a prodrug of the classic antiviral drug cidofovir. It exerts its antiviral effects as an alternative substrate inhibitor of viral DNA replication and is the first smallpox antiviral drug approved by the US FDA for use in all age groups.
Tecoviride is a small molecule virus inhibitor against orthopoxviruses including variola virus and monkeypox virus The virus has strong activity. Its pharmacological effect is to inhibit the replication of viral DNA, and prevent the intracellular virus from being “encapsulated” on the endoplasmic reticulum or Golgi apparatus, so that the virus cannot be released from the cell, reducing the probability of infecting other normal cells, so as to achieve therapeutic effects.
In 2015, an animal trial demonstrated that Tecoviride significantly reduced symptoms and reduced mortality in monkeypox-infected long-tailed macaques [6].
In the latest study, published in The Lancet, 3 monkeypox patients Transaminases increased during the course of taking Tembexa, so the use of Tembexa was terminated; 1 patient with monkeypox took tecavire, no adverse reactions were found during the treatment, and the length of hospital stay was significantly shorter than taking Tembexa and no treatment. patients on antiviral therapy.
This study provides some indication that tecavivir is effective in monkeypox patients, but given the sample size This conclusion is limited and needs to be supported by the results of clinical studies with a higher level of evidence. The researchers also said that there is an urgent need for prospective studies of antiviral drugs for monkeypox.
Does the smallpox vaccine work against monkeypox?
In May 1980, the World Health Organization announced that the smallpox virus had been completely eliminated from mankind, and subsequently, the smallpox vaccine The inoculation work is gradually discontinued.
It was from this time that monkeypox virus began to spread in various regions. Therefore, some scientists believe that The emergence of monkeypox virus was closely related to the termination of the smallpox vaccination effort.
Andrea McCollum, head of the poxvirus team at the US Centers for Disease Control and Prevention, said in an interview with Nature that monkeypox is a rapid The fact of the spread is deeply worrying. Since the eradication of smallpox in the 1970s, public health officials around the world have stopped recommending vaccination against smallpox, and over time, more and more people have become generally susceptible to the virus.
A few days ago, many domestic media quoted the WHO publicPublished data show that smallpox vaccine is 85% effective against monkeypox virus.
85% of this data comes from a 1988 article published in the International Journal of Epidemiology Retrospective study. The study analyzed Zaire monkeypox data over a five-year period from 1980 to 1984, assessing the protection afforded by past smallpox vaccinations and the potential for transmission of the virus in unvaccinated communities.
The researchers used the presence or absence of vaccination scars as the basis for judging whether or not to vaccinate. Data indicate that smallpox vaccination provides approximately 85% protection against monkeypox.
They predict that monkeypox virus will continue to be introduced into human communities from animal sources, and monkeypox epidemics will continue as vaccine protection declines in the population The average size and duration will also increase. On the other hand, current evidence suggests that the virus is significantly less transmissible than smallpox, and that it does not persist in human communities even in the complete absence of vaccination.
So, does this mean that the smallpox vaccine that has been available before can directly help us deal with monkeypox outbreaks?
Actually, in order for a vaccine to be approved, it needs a rolling review by the expert team of the Center for Drug Evaluation of the State Food and Drug Administration. On this basis, a comprehensive and detailed review of the research data submitted by the applicant to support the market, including pharmacy, pharmacology and toxicology, phase I, phase II clinical trials, and Phase III clinical trials conducted domestically or overseas.
Although the smallpox vaccine before 1980 has been approved for the prevention and control of smallpox virus, some of the original data have been changed after the main body of the virus has changed. Can not be used, need new experimental data. The 85% here is not a standardized clinical research data. Therefore, it is for reference only and cannot be used as data for the approval of monkeypox vaccines.
However, if the smallpox vaccine is to be re-applied for monkeypox prevention, at least the safety and quality of the vaccine are controllable After passing the test, the research can focus on the effectiveness data, and the approval process will be faster.
Up to now, the variola virus vaccine has been developed to the third generation, among which the second generation vaccine ACAM2000 and the third generation vaccine IMVAMUNE are effective in preventing monkeypox. The efficacy of infection and post-exposure vaccination has been supported by some preclinical and clinical studies[8,9].
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On May 19, the world’s first monkeypox quarantine order was announced. According to Belgian Evening News, Brussels Times and other reports, the Belgian health department issued a statement on May 19, local time, requiring monkeypox cases to self-isolate for 21 days. For high-risk contacts, such as roommates or intimate partners of a confirmed case, isolation is not required, but should be monitored closely for symptoms.
On May 24, Moderna said it was developing an mRNA monkeypox vaccine. And according to Reuters, the United Kingdom has begun to provide smallpox vaccine to some medical workers or people at risk of exposure to the monkeypox virus.
On July 22, the European Medicines Agency recommended that the European Union approve the expansion of a smallpox vaccine to Prevent monkeypox and block the spread of the virus.
In addition, detection tools for monkeypox are also being developed. According to the news released by the Russian “Vector” National Science Center for Virology and Biotechnology, the center has developed an automatic detection kit for the detection of orthopox viruses such as monkeypox and vaccinia. Laboratory testing has been successfully completed. (Planning: z_popeye | Producer: gyozua)
Acknowledgments: This article has been professionally reviewed by Zhu Yongzhang, Associate Professor, School of Global Health, Shanghai Jiaotong University School of Medicine-National Center for Tropical Diseases ResearchThanks to Song Shijian, Ph.D. Contributions
Source of caption: WHO video screenshot
References:< /span>
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[2]Ladnyj I D, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo[J]. Bull World Health Organ, 1972, 46(5) : 593-597.
[3]Erez N, Achdout H, Milrot E, Schwartz Y, Wiener-Well Y, Paran N, et al. Diagnosis of Imported Monkeypox, Israel, 2018[J]. Emerg Infect Dis, 2019, 25(5): 980-983.
[4]McCollum A M, Damon I K. Human monkeypox[J ]. Clin Infect Dis, 2014, 58(2): 260-267.
[5]Jezek Z, Szczeniowski M, Paluku K M, Mutombo M. Human monkeypox: clinical features of 282 patients[J]. J Infect D is, 1987,156(2): 293-298.
[6]Berhanu A, Prigge J T, Silvera P M, Honeychurch K M, Hruby D E, Grosenbach D W. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection[J]. Antimicrob Agents Chemother, 2015, 59(7): 4296-4300.
[7]Jezek Z, Grab B, Paluku K M, Szczeniowski M V. Human monkeypox: disease pattern, incidence and attack rates in a rural area of northern Zaire[J]. Trop Geogr Med, 1988, 40(2): 73-83.
[8]Petersen B W, Kabamba J, McCollum A M, Lushima R S, Wemakoy E O, Muyembe T J, et al. Vaccinating against monkeypox in the Democratic Republic of the Congo[J]. Antiviral Res, 2019, 162171-177.
[9]Keckler M S, Salzer J S, Patel N, Townsend M B, Nakazawa Y J, Doty J B, et al. IMVAMUNE((R)) and ACAM2000((R)) Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model[J]. Vaccines (Basel), 2020, 8(3).