Monkeypox: epidemiology, pathogenesis, treatment and prevention

Abstract

Monkeypox is a zoonotic disease that was once endemic in west and central Africa caused by monkeypox virus. However, cases recently have been confirmed in many nonendemic countries outside of Africa. WHO declared the ongoing monkeypox outbreak to be a public health emergency of international concern on July 23, 2022, in the context of the COVID-19 pandemic. The rapidly increasing number of confirmed cases could pose a threat to the international community. Here, we review the epidemiology of monkeypox, monkeypox virus reservoirs, novel transmission patterns, mutations and mechanisms of viral infection, clinical characteristics, laboratory diagnosis and treatment measures. In addition, strategies for the prevention, such as vaccination of smallpox vaccine, is also included. Current epidemiological data indicate that high frequency of human-to-human transmission could lead to further outbreaks, especially among men who have sex with men. The development of antiviral drugs and vaccines against monkeypox virus is urgently needed, despite some therapeutic effects of currently used drugs in the clinic. We provide useful information to improve the understanding of monkeypox virus and give guidance for the government and relative agency to prevent and control the further spread of monkeypox virus.

Fig. 1

Geographical distribution of confirmed monkeypox cases during the outbreak between January and September 2022. Confirmed cases include those laboratory-confirmed as monkeypox virus and may include cases only confirmed as orthopoxvirus. Data presented as of 12 September 2022 were obtained from CDC. Diagram generated with GraphPad Prism 9

Fig. 2

Schematic illustration of the transmission and clinical characteristics of monkeypox. There are many modes of transmission, animals infected with monkeypox virus (such as squirrels, rodents, monkey, and sooty mangabey), direct contact with body fluids or diseased parts of infected animals, scratching or biting by animals, consumption of meat from infected animals, sexual contact (MSM), and contact with contaminated objects, respiratory secretions from those infected individuals, skin lesions, along with their bedding and clothing. The clinical characteristics of monkeypox are depicted on the right side of the figure. General features such as lymphadenopathy, fever, headache, chills and/or sweats, sore throat, muscle ache, lack of energy, rash, and genital rashes are seen commonly. Complications of monkeypox include pneumonitis, encephalitis, keratitis, and secondary bacterial infections

Fig. 3

Monkeypox life cycle and mechanisms of action of antivirals. This diagram depicts the life cycle of monkeypox virus inside a human cell. Notably, Replication cycle of monkeypox virus occurs in the cytoplasm of the host cell. Following viral attachment, virion binds and fuses with the host cell membrane, the viral core is released into the cytoplasm of the host cell. Viral particles are assembled into intracellular mature viruses (MV), then stay in the cytoplasm as intracellular mature virions of released as extracellular enveloped viruses during cell lysis. MV can also wrap an additional envelope and attached to the cell membrane, then then release through exocytosis. Cidofovir and its prodrug brincidofovir inhibit the viral DNA polymerase during DNA replication. Tecovirimat targets the VP37 protein, which is vital for envelopment of intracellular mature virus with Golgi-derived membrane to form enveloped virus (EV), prevents the virus from leaving an infected cell, hindering the spread of the virus within the body

Fig. 4

Development of monkeypox vaccines in the future. Currently, live attenuated vaccines such as ACAM2000 and JYNNEOS are clinically recommended for the prevention of monkeypox, but these vaccines were originally designed to prevent smallpox. Therefore, there is a demand for the development of vaccines that specifically prevent monkeypox, such as inactivated vaccines, DNA vaccines, RNA vaccines, and recombinant protein vaccines. These types of vaccines have proven their efficacy and safety in the COVID-19 epidemic