2. Etiology and pathogenesis
The mpox virus exists in two main clades, clade I and clade II, which differ in virulence and severity [4]. Clade I, primarily endemic in the Democratic Republic of Congo, is associated with a significantly higher case fatality rate. A sub-lineage, clade Ib, has recently emerged in Africa and has shown a greater capacity for transmission, with outbreaks also documented in European school
settings. [12] Clade II, originating from West Africa, was the main cause of the 2022 outbreak. Transmission occurs through direct contact with bodily fluids, skin lesions, or contaminated materials (fomites). Contagion can also happen via respiratory droplets during prolonged contact. Recent evidence suggests a significant role for sexual transmission in the current spread of the
virus [5]. The mpox virus is a double-stranded DNA virus. It is quite large for a virus, measuring approximately 200 nm in width and 300-400 nm in length. This exceptional size makes it, along with other giant viruses like the human smallpox virus, visible and studyable under a light microscope [11], unlike most other human viruses that require the use of an electron microscope due to their significantly smaller size.

3. How sexual transmission was proven and post-recovery risks
The sexually transmissible nature of monkeypox was understood through a combination of converging clinical, epidemiological, and virological evidence:
 Epidemiological evidence. The 2022 outbreak showed a pattern of spread closely linked to social networks, with a concentration of cases among men who have sex with men (MSM)
[6]. Outbreaks occurred in social settings and festivals, suggesting that intimate and sexual contact was the main route of propagation.
 Clinical evidence. A significant number of patients developed skin lesions (papules, vesicles, pustules) concentrated in the genital, perianal, and oral areas, which are the most common points of contact during sexual intercourse [7].
 Virological evidence. Laboratory studies detected viral DNA of the mpox virus in bodily fluids, including semen and rectal fluids. This confirmed that the virus can be carried and transmitted through these routes.
Risks after recovery. A crucial aspect that makes monkeypox a dangerous infection even after the visible symptoms have resolved is viral persistence [8]. Although the viral load in skin lesions decreases with healing, the virus's DNA can remain detectable in semen for weeks, and in some cases up to 39 days after symptom onset. While the detection of viral DNA does not always equate to the presence of an infectious virus, in some studies, "replication-competent" virus was isolated from the semen of patients. For this reason, health authorities, such as the World Health Organization (WHO), recommend using condoms for at least 12 weeks after complete recovery to prevent transmission.

4. Epidemiology
From January 2022 to January 2025, there were 129,523 confirmed cases of monkeypox registered globally, with 283 deaths [9]. The distribution of deaths reflects the different lethality of the viral strains:
 The vast majority of deaths occurred in Africa, where the Clade I strain circulates, known to have an estimated mortality rate of between 4% and 10%.
 In contrast, in the Americas and Europe, where the Clade II strain has prevailed, the case fatality rate has been significantly lower, less than 1%.

5. Clinical manifestations and diagnosis
The disease has an incubation period ranging from 5 to 21 days. Initial symptoms are often non- specific and include fever, headache, myalgia, and, in particular, lymphadenopathy (swollen lymph nodes) [10]. Subsequently, a skin rash appears, which begins as a flat spot and progresses through distinct stages:
 Macules (flat lesions)
 Papules (raised lesions)
 Vesicles (clear fluid-filled lesions)

 Pustules (pus-filled lesions)
 Crusts (lesions that dry up and fall off)
The lesions are often concentrated in the genital, perianal, and oral areas, highlighting the route of sexual transmission. Diagnosis is confirmed via PCR (polymerase chain reaction) on a sample taken from the skin lesions.

6. Treatment and prevention
Most cases of monkeypox are self-limiting, but complications can occur in immunocompromised individuals. Treatment is based on antiviral drugs, such as tecovirimat, which blocks virus replication. Prevention is based on two pillars:
1. Vaccination. The use of third-generation vaccines (such as JYNNEOS) is recommended for at-risk individuals, including close contacts of confirmed cases and healthcare workers.
2. Public Health Measures. Case isolation, contact tracing, and public education, particularly on sexual health and low-risk practices, are crucial for containing the spread.

7. Conclusions and future perspectives
Monkeypox represents an example of how a previously controlled pathogen can re-emerge due to changes in demographics, population immunity, and human behavior, becoming a new sexually transmitted infection. Future challenges include the development of more accessible vaccines and treatments, improved surveillance in endemic areas, and a coordinated global strategy to prevent future pandemics.

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*Board Member, SRSN (Roman Society of Natural Science)
Past Editor-in-Chief, Italian Journal of Dermosurgery