Unusual global outbreak of monkeypox: what should we do?

doi:10.1007/s11684-022-0952-z

Front. Med.

2022, Vol. 16

Issue (4) : 507-517 https://doi.org/10.1007/s11684-022-0952-z

REVIEW

Unusual global outbreak of monkeypox: what should we do?

Miaojin Zhu¹, Jia Ji¹, Danrong Shi¹, Xiangyun Lu¹, Baohong Wang^1,², Nanping Wu^1,², Jie Wu^1,²(

), Hangping Yao^1,²(

), Lanjuan Li^1,²(

)

¹. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
². Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China

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Abstract

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.

Keywords monkeypox poxviruses vaccine infectious diseases

Corresponding Author(s): Jie Wu,Hangping Yao,Lanjuan Li

About author: Tongcan Cui and Yizhe Hou contributed equally to this work.

Just Accepted Date: 13 July 2022 Online First Date: 09 August 2022 Issue Date: 02 September 2022

Cite this article:

Miaojin Zhu,Jia Ji,Danrong Shi, et al. Unusual global outbreak of monkeypox: what should we do?[J]. Front. Med., 2022, 16(4): 507-517.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0952-z
https://academic.hep.com.cn/fmd/EN/Y2022/V16/I4/507

Fig.1 Structure and genome of monkeypox virus. The top left and right parts of the figure show the structures of enveloped virions (EVs) and mature virions (MVs) respectively. EVs have an extra envelope than MVs. The surface of the outer membrane consists of irregularly shaped tubules. The interior of the viral particle consists of a dumbbell-shaped nucleus and a pair of the lateral bodies between the concavities and the outer membrane. The bottom part of the figure shows the genome of the monkeypox virus (data from ViralZone, SIB Swiss Institute of Bioinformatics). It is approximately 197 kb of double-stranded DNA and contains an inverted terminal repeat (ITR) sequence at the end of the genome. In the central region of the genome are mostly genes encoding necessary replication enzymes and structural proteins of the virus, which are highly homologous compared to the smallpox virus.

Fig.2 Transmission routes and clinical symptoms of human monkeypox. The section on the left describes how the monkeypox virus is transmitted. Animals such as monkeys, rodents, and patients infected with monkeypox virus can be the source of infection. There are many modes of transmission: animal bites, respiratory droplets, sexual contact, and contact with body fluids of infected animals or patients. The section on the right describes the clinical signs of human monkeypox. Monkeypox virus infection can involve multiple body systems and is characterized by a centrifugal rash. The rash changes from macular papules to small blisters and pustules. Scabs formed after approximately 10 days and disappeared after approximately 3 weeks. Some patients with monkeypox have enlarged lymph nodes in the neck (submandibular and cervical), axillae, or groin during the rash phase, which is the clinical feature that distinguishes monkeypox from smallpox. This figure was drawn using Figdraw, an open access online scientific research drawing platform.

Name	Manufacturer	Mechanism of action	Administration and dosage	Clinical trial information	Indications and usage	References
Antiviral therapeutics
Tecovirimat	SIGA Technologies	Inhibits the activity of the orthopoxvirus VP37 envelope wrapping protein and prevents virus replication and intracellular viruses release	PO, IVAdults: 600 mg twice daily for 14 daysPediatrics (13 kg or more): dosage reduction	The completed phase 3 clinical trials to evaluate the safety, tolerability, and pharmacokinetics of tecovirimat showed the drug was safe with minor side effects	Licensed by FDA for the treatment of human smallpox disease since July 2018 and urgently licensed by FDA for treatment of monkeypox in 2022	[61,62]
Brincidofovir	Chimerix	Phosphorylated cidofovir diphosphate acts as a competitive substrate inhibitor of DNA polymerase to reduce DNA synthesis and terminating chain elongation	POMost frequently administered at an oral dose of 200 mg twice weekly	The completed phase 1/2/3 clinical trials showed the drug had effective antiviral effects and the main dose-limiting toxic effects are gastrointestinal events	Licensed by FDA for treatment of human smallpox disease in adult and pediatric patients in the US since June 2021	[63,64]
Cidofovir	Gilead	Inhibits CMV replication by selective inhibition of viral DNA polymerase, thereby preventing viral replication and transcription	IV5 mg/kg once weekly for the first 2 weeks, and thereafter once every other week	The completed phase 2/3 clinical trials to evaluate the effectiveness, safety of cidofovir in AIDS patients with CMV retinitis showed the drug was effective, but with the potential risk of nephrotoxicity	Developed for the treatment of cytomegalovirus retinitis in patients with AIDS, which has been used in the treatment of poxvirus infections	[65–67]
Blood products
Vaccinia Immune Globulin	Cangene Corporation/ DynPort Vaccine	Antibodies isolated from blood of healthy adults vaccinated with vaccinia neutralize the virus to inhibit viral infection and provide passive immunity	IVSevere complications of vaccinia vaccination: 6000 U/kg with a maximum speed of 2 mL/min as soon as symptoms appearPersistent or severe symptoms: considered repeated administration	An open-label phase 4 study is under way to collect additional data to assess the safety and efficacy of VIGIV in healthy people	Licensed by FDA for the treatment of complications caused by vaccinia vaccination since February 2005, considered emergency treatment of orthopoxviruses in the case of a serious outbreak	[68,69]
Vaccines
MVA-BN	Bavarian Nordic	Based on a live, highly attenuated vaccinia virus, unable to achieve complete replication in humans but can induce an effective immune response	IHA total of 2 doses (0.5 mL per dose) were injected subcutaneously with an interval of 4 weeksSubjects previously vaccinated against smallpox: a single 0.5 mL dose	The completed phase 2/3 clinical trials showed it had excellent safety and tolerability in both healthy and low immunity people, and its immunogenicity was not inferior to ACAM2000	Licensed by FDA to prevent monkeypox in September 2019, applicable to adults over 18 years old with high risk of monkeypox infection	[70–73]
ACAM2000	Acambis	A live, replication-competent vaccinia virus vaccine derived from a plaque-purified clone can induce an effective immune response	TDDAdministered in a single 2.5 μL dose by the percutaneous route (scarification) using 15 jabs bifurcated needle to the deltoid muscle of the upper arm	The completed phase 1/2/3 clinical trials have shown it had excellent immunogenicity and safety, but with the concerns about the incidence of vaccination-related myopericarditis	Licensed by FDA for people at high risk of exposure to smallpox since August 2007	[70,74,75]
APSV	Aventis Pasteur	A liquid formulation of calf-lymph vaccine produced by vaccinia virus derived from the NYCBOH strain can induce an effective immune response	TDDAdministered in a single 2.5 μL dose by the percutaneous route (scarification) using 15 jabs bifurcated needle to the deltoid muscle of the upper arm	The completed phase 1/2 clinical trials to evaluate the safety, dose and preliminary efficacy of APSV in vaccinia-naive adults showed it was still effective at diluted doses, but its reactogenicity did not decrease	Submitted a pre-EUA to FDA for the use of APSV diluted 1:5 to vaccinate persons during a declared public health emergency involving smallpox	[70,76]
Tiantan	Sinopharm	A live, highly attenuated vaccinia virus isolated from the blister scab of patients with smallpox in 1926 can induce an effective immune response	TDDAdministered in a single 10 μL dose by the acupuncture or scarification route inoculation on the deltoid muscle of the upper arm	The completed phase 2 clinical trials of recombinant Tiantan vaccinia virus-vectored/HIV-1 booster in healthy people showed excellent performance in immunogenicity and safety	Licensed for use in China. Novel smallpox vaccines constructed by deleting some genes of Tiantan strain, have been used in the research of vaccines such as HIV, HBV, HCV and so on	[77–80]

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