Following the World Health Assembly declaring the eradication of smallpox in 1980, public health agencies ended most smallpox vaccination campaigns, which inadvertently reduced the population’s resistance to various orthopoxviruses, including mpox. As of August 20, 2024, over 17,000 suspected cases of mpox were reported throughout Africa, most of which occurred in the Democratic Republic of the Congo (DRC).
The widespread transmission of mpox is accompanied by a significant shortage of both treatment kits and vaccines in the DRC. Thus, there remains an urgent need to coordinate an international response that will increase assistance to the region in treating current patients and avoiding the further spread of this viral outbreak.
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Understanding Mpox
Virus Overview
Originally identified in 1958, mpox is a deoxyribonucleic acid (DNA) virus that belongs to the Poxviridae family of the Orthopoxirus genus. The first documented mpox infection in a human was reported in 1970 in a nine-year-old child in the DRC2.
Like other orthopoxviruses, mpox consists of a central conserved region, as well as reverse terminal repeats with tandem repeats. The mpox virus can exist either as an intracellular mature virus or an extracellular envelope virus. After attachment and subsequent fusion with the host cell membrane, the enveloped mpox virus leaves the infected host cell through exocytosis.
Transmission
Although rodents are considered the natural host of mpox, this virus has a wide host range, including monkeys, squirrels, and prairie dogs2. The primary route of animal-to-transmission is through contact with the blood, bodily fluids, skin, or mucous membranes, as well as a bite or scratch from an infected animal. Likewise, human-to-human transmission arises following contact with blood, bodily fluids, or the contaminated materials of an infected individual.
As compared to previous mpox outbreaks, the current transmission of infections has significantly accelerated, affecting at least four previously unaffected African countries: Kenya, Rwanda, Uganda, and Burundi1. Sporadic cases and outbreaks have also been reported in countries outside of Africa, most of which have been attributed to individuals returning from travel to endemic regions or the importation of infected animals4.
Whereas mpox was primarily transmitted through sexual contact among men who have sex with men (MSM) during the 2022 epidemic, the current mpox outbreak has mainly affected children, with clusters of mpox cases attributed to sexual contact.
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Symptoms and Diagnosis
Clinical features
Following the initial infection, mpox has an incubation period that can range from three to twenty days, which is followed by the development of rash symptoms that can persist for up to five weeks. The rash that is commonly associated with mpox infection begins as macules and will eventually transition to papules and blisters before crusting over. This rash often starts on the face, where it will typically spread to the trunk, hands, feet, and other regions throughout the body2.
In addition to this hallmark rash, mpox infection may also lead to fever, headache, lethargy, swollen lymph nodes, weakness, and muscle pain. Severe mpox infection may also lead to bronchopneumonia, eye and skin lesions, and sepsis.
Diagnostic Methods
Both direct and indirect tests can be used to confirm mpox infection. The most commonly employed direct laboratory tests include nucleic acid amplification tests (NAATs), which are used to identify mpox DNA sequences present within clinical specimens5.
Comparatively, the indirect diagnosis of mpox infection often involves serological tests, including enzyme-linked immunosorbent assay (ELISA), lateral flow assays (LFAs), plaque reduction neutralization testing (PRNT), and immunohistochemistry (IHC). These immune-based assays are limited in their utility for mpox diagnosis, as they are not capable of differentiating between different orthopoxvirus species.
Recent Resurgence
There are two clades of mpox, which include clade I and clade II. The current mpox outbreak, which began in 2022, is due to clade II mpox transmission. Clade II mpox infection is considered to be less severe than clade I infections, as 99% of people have survived infection during the current outbreak3.
Nevertheless, of the over 102,000 clade II mpox infections that have been reported since 2022, 222 deaths have been attributed to this disease.
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Impact on Public Health
Health Risks
As compared to the general population, where the risk of mpox transmission is low, MSM is considered to be at an increased risk of mpox infection. The MSM-associated risk was evident during the 2022 outbreak, as many of the individuals infected with mpox did not recently travel to endemic regions in Central and Western Africa.
Children, immunocompromised individuals, as well as those with pre-existing conditions, are at an increased risk of severe disease following mpox infection. This is particularly important in the context of MSM, as the presence of human immunodeficiency virus (HIV) may increase the severity of mpox infection and vice versa.
There remains a lack of research on the pathogenesis of co-infection with both mpox and HIV; therefore, further studies are needed to develop effective treatment and preventive strategies, particularly for the MSM community.
Public Health Measures
The United States Food and Drug Administration (FDA) has approved JYNNEOS, a Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine originally developed to prevent smallpox against mpox in adults. Although a single dose of MVA-BN has been associated with up to 86% efficacy, current recommendations are for eligible individuals to receive two doses within four weeks4.
In the U.S., individuals with suspected exposure to mpox, those who previously had a sexual encounter with an mpox-infected individual, or gay, bisexual, or MSM, as well as transgender, nonbinary, or gender-diverse individuals who have been diagnosed with a sexually transmitted disease (STD) in the past six months, are currently eligible for mpox vaccination.
Future Directions
Despite the availability of MVA-BN vaccines, the efficacy of vaccination is limited following exposure to mpox. Thus, there remains an urgent need to develop new vaccines, as well as antiviral drugs and robust diagnostic tools, to prevent the further spread of mpox.
Additional research is also needed to elucidate the different mechanisms mpox utilizes to persist in the environment.
References
- Rivers, C., Watson, C., & Phelan, A. L. (2024). The Resurgence of Mpox in Africa. JAMA. doi:10.1001/jama.2024.17829.
- Luo, Y., Zhang, T., Cao, J., et al. (2024). Monkeypox: An outbreak of a rare viral disease. Journal of Microbiology, Immunology and Infection 57(1); 1-10. doi:10.1016/j.jmii.2023.12.006.
- “Ongoing Clade II Mpox Global Outbreak” [Online]. Available from: https://www.cdc.gov/mpox/outbreaks/2022/index-1.html.
- Acharya, A., Kumar, N., Singh, K., & Byrareddy, S. N. (2024). Mpox in MSM: Tackling Stigma, Minimizing Risk Factors, Exploring Pathogenesis, and Treatment Approaches. Biomedical Journal. doi:10.1016/j.bj.2024.100746.
- Ribeiro da Silva, S. J., Kohl, A., Pena, L., & Pardee, K. (2023). Clinical and laboratory diagnosis of monkeypox (mpox): Current status and future directions. iScience 26(6). doi:10.1016/j.isci.2023.106759.
Further Reading