What is Mpox?
Mpox, formerly known as monkeypox, is a viral zoonosis caused by the Mpox virus, a member of the Orthopoxvirus genus of the Poxviridae family. . This virus shares genetic and morphological characteristics with the variola virus, which has been eradicated. The Mpox virus has a double-stranded DNA genome and carries out its replication cycle in the cytoplasm of host cells. Transmission to humans can occur through direct contact with infected animals, contaminated materials, or from person to person. The disease is characterized by fever, headache, muscle aches, and a distinctive rash that spreads over the body. In terms of public health, Mpox is monitored globally due to its potential to cause outbreaks in urban areas and its relevance to research in viral genomics and epidemiology.
The Mpox virus that causes Mpox is not a variant of the smallpox virus, but rather a distinct virus within the same genus Orthopoxvirus. . Mpox was first identified in 1958 during an outbreak of a smallpox-like disease in monkeys kept for research, hence the name “monkeypox”. The first human case was subsequently documented in the Democratic Republic of the Congo in 1970. Although related, Mpox and smallpox viruses have distinct natural reservoirs and epidemiological characteristics. Mpox is most commonly associated with rodents and small mammals in Africa, which are considered the natural reservoir of the virus. Transmission to humans occurs most frequently in close proximity to wildlife, especially in rural and forested areas where humans come into direct contact with infected animals. Thus, Mpox did not arise as a “variant” of the smallpox virus, but rather as a separate pathogen that has always existed in its animal reservoirs, manifesting in humans under specific conditions of zoonotic exposure. Occasional confusion between the two is due to the clinical similarity of the diseases they cause and the fact that they are both orthopoxviruses.
In 2022, the World Health Organization (WHO) renamed “monkeypox” to “Mpox” as part of an effort to avoid stigmatization and inaccuracies in the naming of the disease. Thus, “Mpox” and “monkeypox” refer to the same viral disease caused by the Mpox virus. Originally called “monkeypox” due to an outbreak in laboratory monkeys, this designation was somewhat misleading because monkeys are not the natural reservoir of the virus; rodents are considered the more likely reservoir. The name change to “Mpox” was an effort to better align the name with the nature of the disease and its epidemiological context, as well as to reduce the potential for discrimination associated with the old name.
How does Mpox attack the body?
Mpox infection begins when the virus enters the body, usually through a break in the skin, mucous membranes (such as the eyes, mouth, or nose), or by inhalation. The virus has a tropism, or preference, for cells in the skin and lymphatic system, where it multiplies and triggers an initial immune response.
How Mpox Attacks the Body and What It Attacks
- Entry and Incubation : After entry, the virus goes through an incubation period ranging from 5 to 21 days, during which there are still no symptoms.
- Invasion (Prodromal) Phase : Initial symptoms include high fever, severe headache, lymphadenopathy (enlarged lymph nodes), back pain, muscle aches, and severe asthenia (weakness). These symptoms reflect the initial viral spread and systemic inflammatory response.
- Rash and Progression : Within 1 to 3 days of the onset of fever, a rash begins to appear, initially on the face and then spreading to other parts of the body. The lesions progress from macules ( spots ) to papules (raised bumps ) , vesicles (fluid-filled blisters), pustules, and finally crusts.
Evolution of Symptoms
- Vesicle / Pustule Stage : The most contagious and clinically significant stage is when vesicles and pustules are present. These lesions are painful and can cause permanent scarring .
- Resolution : Resolution begins when the scabs fall off. The total period of illness varies, but may last 2 to 4 weeks.
Important Considerations
- Contagion : Transmission can occur through direct contact with bodily fluids or skin lesions of an infected person, or through contaminated materials such as clothing or bedding.
- Severity and Treatment : Severity can vary; severe cases are more common in children and immunocompromised individuals. Treatment is primarily supportive, but specific antivirals and vaccinia-based vaccines may be considered in severe cases or in high-risk groups.
The lethality of Mpox can vary significantly depending on the strain of the virus, the geographic location of the outbreak, public health conditions, and access to medical care. There are two main strains of the Mpox virus, which differ in their virulence:
- West African strain : This strain is considered less virulent, with a case fatality rate of around 1% in populations not vaccinated against smallpox.
- Congo Basin strain ( Central Africa) : This strain is more severe, with a fatality rate that can reach around 10% in unvaccinated populations.
During outbreaks in areas with better health infrastructure and access to medical care, the case fatality rate tends to be lower. In recent outbreaks outside Africa, including the expanded outbreaks of 2022 in several non-endemic countries, the case fatality rate has been extremely low, with few deaths reported relative to the total number of cases. The availability of supportive care, antiviral treatments, and preventive measures such as vaccination for high-risk contacts contribute to reducing the severity and case fatality of the disease in these areas.
Neurobiology related to Mpox
The relationship between neurobiology and Mpox infection is a field that still requires in-depth research, but as with many viruses that have systemic impact, there are possible interactions and neurological consequences associated with infection. Here are some considerations on how Mpox may be related to neurobiology:
1. Invasion of the Central Nervous System (CNS)
Although rare, there is a possibility that the Mpox virus can invade the central nervous system. This can occur if the virus crosses the blood-brain barrier, a highly selective membrane that protects the brain from pathogens. Viral infections that reach the CNS can cause meningitis, encephalitis, or other serious neurological conditions.
2. Immune Response and Neuroinflammation
The immune response to the virus can lead to neuroinflammation, even if the virus does not directly invade the CNS. Systemically released pro-inflammatory cytokines and inflammatory mediators can affect the brain, potentially causing neuropsychiatric symptoms such as mood swings, confusion, or difficulty concentrating. These effects are usually temporary but highlight the interplay between systemic infection and neurological health.
3. Indirect Neurological Complications
Neurological complications can arise indirectly as a result of the body’s response to the virus. For example, a severe infection can result in an exaggerated immune response or sepsis, which in turn can affect neurological functioning.
4. Case Studies and Reports
Case reports and studies documenting neurological effects associated with Mpox are limited but essential to better understand the disease. Monitoring neurological symptoms in patients with Mpox may help identify patterns of neurological manifestations associated with the disease.
Relationship between genetic predisposition and risks
The relationship between genetic predisposition and the risk of contracting or developing severe forms of Mpox is still in the early stages of investigation, given the relative novelty and complexity of recent outbreaks. However, studies in other viral infections and understanding of immunology suggest that genetic factors may influence susceptibility to and severity of infectious diseases, including Mpox. Here are some key areas where genetic predisposition may play a role:
1. Innate and Adaptive Immune Response
The effectiveness of the immune response, both innate and adaptive, is crucial to controlling viral replication and eliminating the virus. Genetic variations in genes encoding immune system proteins, such as pattern recognition receptors (PRRs) that detect pathogens, and components of immune signaling pathways, may affect an individual’s ability to mount an effective response against Mpox virus.
2. Cytokine Expression
Cytokines play essential roles in regulating the inflammatory response against infections. Polymorphisms in genes that regulate the production of cytokines, such as IL-10, TNF-α, and IFN-γ, may influence the severity of the inflammatory response, leading to differences in disease progression and clinical outcomes between individuals.
3. Skin Integrity and Mucosal Barriers
Genetic differences affecting skin and mucosal integrity may alter susceptibility to skin infections and pathogen entry. Genes involved in the regulation of skin repair, dermal inflammatory response, and mucosal barrier maintenance may be relevant.
4. Specific Resistance and Susceptibility
Studies of other viral diseases have identified specific genetic loci associated with resistance or susceptibility to certain viruses. Future research could identify similar markers for Mpox, especially considering that inter-individual variation in disease severity suggests a possible genetic component.
Treatment
Treatment of Mpox is primarily supportive, aimed at relieving symptoms and preventing complications. In severe cases or in patients at high risk of complications, such as immunocompromised individuals, antiviral treatments may be considered. Tecovirimat (TPOXX) is an FDA-approved drug specifically for the treatment of smallpox, but has been used against Mpox under compassionate or emergency use protocols. In addition to tecovirimat, cidofovir and brincidofovir, antivirals originally developed for the treatment of cytomegalovirus infections, may also be used. Symptomatic treatment includes administration of analgesics and antipyretics to manage pain and fever. Vaccinia-based vaccines, such as JYNNEOS in the United States, are also used preventively in individuals at high risk of exposure to the virus. Appropriate management of patients requires a multidisciplinary approach, with continuous monitoring to assess response to treatment and the emergence of possible side effects.
