Atypical monkeypox begins to spread. Will it wreak havoc around the world like the new coronavirus? | Wolters Kluwer Medical Frontier

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This monkeypox outbreak has swept more countries or regions where monkeypox is not endemic, and obvious human-to-human transmission routes have emerged. Sexual contact has also become an important mode of transmission and is spreading rapidly. This atypical outbreak has sounded the alarm for the global public health system. Will it be as rampant as the new coronavirus?

Written by Wang Huifang (The Fifth Medical Center of PLA General Hospital)

Monkeypox virus is a close relative of smallpox and cowpox virus, both of which belong to the Poxviridae family. Since smallpox was eradicated in the 1980s, monkeypox virus has become the orthopoxvirus with the greatest impact on public health, mainly prevalent in central and western Africa. However, starting from May 7, 2022, monkeypox cases were reported in several countries outside Africa. As early as May 21, the World Health Organization (WHO) stated that this monkeypox epidemic had spread from person to person, which was an "atypical" phenomenon. The latest data from the US CDC shows that as of July 15, there have been at least 1,814 suspected or confirmed cases in the United States, and a total of 68 countries around the world have reported 12,556 confirmed cases. [1]

In response to this outbreak, the team led by Academician Wang Fusheng from the Fifth Medical Center of the General Hospital of the Chinese People's Liberation Army published a review paper titled "Human Atypical Monkeypox: Early warning for global outbreak?" in the journal Infectious Disease & Immunity. The paper briefly summarized the epidemiological and clinical characteristics of the disease and proposed certain clinical management and prevention strategies.

Epidemiological and clinical characteristics

pathogen

Monkeypox virus is an enveloped double-stranded DNA virus belonging to the Poxviridae family, Chordovirinae subfamily, Orthopoxvirus genus, Monkeypox virus species. Under an electron microscope, monkeypox virus is a relatively large brick-shaped particle, about 200-250nm in size[2].

Figure 1 Electron micrograph of monkeypox virus [6]丨Avavable from:
https://www.statnews.com/2022/05/17/cdc-expresses-concern-about-possibility-of-undetected-monkeypox-spread-in-uk/

In 1958, scientists first isolated and identified monkeypox virus in monkeys shipped from Singapore to Denmark. In 1970, the first human case of monkeypox was found in a child in the Democratic Republic of the Congo [3]. Although monkeypox virus was first discovered in monkeys, monkeys are not the main carriers, and African rodents are most likely its natural hosts. Squirrels, Gambian rats, marmots, different species of monkeys, and humans can all be infected with monkeypox virus and become sources of infection [4, 5].

Monkeypox virus has two different genetic evolutionary branches, the Central African branch and the West African branch. During this outbreak, teams from Portugal, Belgium, the United States and other countries tested the genome sequences of the virus and found that they all belonged to the mild West African branch, which is closely related to the monkeypox virus found in the United Kingdom, Singapore and Israel in 2018 and 2019 [6].

spread

Direct contact with infected animals may cause the monkeypox virus to spread from animals to humans. The monkeypox outbreak in the United States in 2003 originated from Gambian giant rats imported from Ghana, which spread domestically through local pet prairie dogs. Human-to-human transmission channels include: contact with respiratory secretions, skin lesions, contact with contaminated objects, or prolonged face-to-face respiratory droplet transmission. In 2018, a British medical worker was also diagnosed with monkeypox after caring for a confirmed case of monkeypox, providing indisputable evidence of human-to-human transmission. On May 21, 2022, the World Health Organization issued a statement saying that human-to-human transmission of monkeypox had occurred among people who had close contact with symptomatic patients[7].

What is particularly noteworthy about this outbreak is that many of the reported monkeypox cases are homosexual, bisexual or other men who have sex with men (MSM), and the case cluster is mainly concentrated in men aged 20-50 years old. Most of them lack immune protection against the monkeypox virus, which makes sexual transmission a focus of attention.

Clinical features and diagnostic principles

Monkeypox is usually an acute, self-limiting disease with symptoms lasting 2 to 4 weeks. The incubation period is 6 to 13 days, with a maximum range of 5 to 21 days. Symptoms include fever, headache, swollen lymph nodes, myalgia (muscle and body pain), back pain, and weakness (extreme weakness). Swollen lymph nodes in the neck, behind the ears, armpits, or inguinal areas are specific signs that distinguish it from smallpox.

The rash first appears on the face and then spreads to other areas. It may develop from macules to papules, blisters, pustules, and finally scabs and fall off [2, 8]. Cases with the above clinical manifestations can be further diagnosed by combining PCR technology to detect monkeypox virus-specific DNA, but they still need to be differentiated from other rash diseases such as smallpox, chickenpox, measles, and syphilis. The overall mortality rate of monkeypox is 8.7%, with significant differences between different branches. Generally speaking, the Central African branch can lead to more serious disease prognosis and a higher mortality rate of about 10.6%, while the mortality rate of the West African branch is about 3.6% [9].

Prevention and treatment

prevention

In order to stop the spread of monkeypox, both confirmed and suspected cases need to be detected, isolated, diagnosed and treated early. Infected people should be strictly isolated until the lesions have scabbed and fallen off, and close contacts should also be isolated and monitored. On May 19, the Belgian health authorities stipulated that monkeypox cases should be self-isolated for 21 days[10].

Orthopoxviruses have cross-reactivity and cross-protection. A previous study showed that the smallpox vaccine is 85% effective against monkeypox and is effective for up to 25 years [5]. Jynneos (also known as Imvamune or Imvanex) is a smallpox vaccine developed by the Danish company Bavarian Nordic. It was approved by the U.S. Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and monkeypox infections. It is currently recommended to adopt a "ring vaccination" strategy for high-risk groups and close contacts, that is, the first ring is composed of close contacts of confirmed cases, and the second ring is composed of secondary close contacts of close contacts. Vaccination of these two rings is prioritized to cut off the transmission route and curb the spread of monkeypox virus [11]. The U.S. Centers for Disease Control and Prevention has stated that vaccination within 4 days after exposure can prevent the onset of the disease, and vaccination within 14 days can reduce the severity of the disease [12].

treat

To date, there is no specific treatment for monkeypox. The clinical treatment principles are symptomatic supportive treatment, control of complications and prevention of sequelae[7].

Tecovirimat, a potent inhibitor of the VP37 protein of orthopoxvirus, was approved by the European Medicines Agency in 2022 for the treatment of smallpox, monkeypox, and vaccinia. Brincidofovir is a DNA polymerase inhibitor approved by the U.S. Food and Drug Administration for the treatment of smallpox and may have some therapeutic effect on monkeypox [5]. A recent retrospective observational study reported that three monkeypox patients treated with Brincidofovir all discontinued treatment due to elevated liver enzymes, while one patient treated with Tecovirimat did not experience adverse reactions and had significantly shortened viral shedding and disease duration [13]. Of course, further clinical studies are still needed to clarify the efficacy and safety of Tecovirimat and Brincidofovir in the treatment of human monkeypox. In addition, immunotherapy based on clinical experience, such as intravenous vaccinia immune globulin, also needs to be supported by clinical experimental data.

Outlook

Over the past 50 years, human monkeypox cases have been increasing slowly, but they have all been transmitted from infected animals to humans in central and western Africa, showing a sporadic epidemic. This time, the monkeypox outbreak has swept more countries or regions where monkeypox is not endemic, and there has been an obvious human-to-human transmission route. Sexual contact transmission has also become an important mode of transmission and is showing a rapid spread. This atypical outbreak has sounded the alarm for the global public health system. Against the backdrop of the new coronavirus pandemic, the emergence of monkeypox has inevitably caused public concern again. However, the monkeypox virus is different from the new coronavirus. The monkeypox virus is a double-stranded DNA virus with a relatively stable structure and a low mutation rate. The basic transmission index R0 of the monkeypox virus is about 0.6-1.0, which means that the possibility of sustained human-to-human transmission is extremely small. The monkeypox virus is transmitted between people through long-term close contact, which makes it easier to control and cut off the transmission route. Moreover, humans have a good understanding of smallpox and monkeypox viruses, and drugs and vaccines against smallpox viruses will also provide a certain reserve capacity for dealing with monkeypox.

According to the WHO's recommendations, strong global surveillance and increased awareness of the disease will help prevent the spread of monkeypox; clinicians need to pay close attention to and monitor possible monkeypox cases, diagnose and isolate them early to prevent further spread, and provide the best clinical care plans; conduct more in-depth research on the biology, epidemiology, transmission and pathogenesis of monkeypox virus, and accelerate the development of corresponding screening reagents, detection technologies and therapeutic drugs to accurately prevent and treat monkeypox. At the same time, my country must also form corresponding clinical diagnosis and treatment plans to further improve the level of immune protection of the population and provide practical and effective protection for the prevention and control of possible monkeypox epidemics.

References

[1] https://www.cdc.gov/

[2] Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis. The Lancet Infectious Diseases 2004;4(1):15-25. doi: 10.1016/s1473-3099(03)00856-9.

[3] Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bulletin of the World Health Organization 1972;46(5):593-7.

[4] Sklenovska N, Van Ranst M. Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans. Front Public Health 2018;6:241. doi: 10.3389/fpubh.2018.00241.

[5] McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis 2014;58(2):260-7. doi: 10.1093/cid/cit703.

[6] A CDC expert answers questions on monkeypox: STAT, 2022 Available from: https://www.statnews.com/2022/05/19/a-cdc-expert-answers-questions-on-monkeypox/.

[7] Disease Outbreak News;Multi-country monkeypox outbreak in non-endemic countries: World Health Organization, 2022 Available from: https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385.

[8] Mahase E. Monkeypox: What do we know about the outbreaks in Europe and North America? BMJ 2022;377:o1274. doi: 10.1136/bmj.o1274.

[9] Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLOS Neglected Tropical Diseases 2022;16(2). doi: 10.1371/journal.pntd.0010141.

[10] First monkeypox quarantine ordered in EU: RT, 2022 Available from: https://www.rt.com/news/555928-belgium-mandatory-quarantine-monkeypox-cases/.

[11] Kozlov M. Monkeypox goes global: why scientists are on alert. Nature 2022;606(7912):15-6. doi: 10.1038/d41586-022-01421-8.

[12] Moore M, Zahra F. Monkeypox. In: StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC.; 2022.

[13] Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. The Lancet Infectious diseases 2022. doi: 10.1016/s1473-3099(22)00228-6.

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