The Monkeypox virus (MPXV), a double-helix DNA virus, has emerged as a significant zoonotic pathogen with the potential for widespread public health implications. Belonging to the Poxviridae family, subfamily Chordopoxvirinae, and the Orthopoxvirus genus, MPXV shares its lineage with other viruses that cause notable diseases, including smallpox, cowpox, and camelpox. First identified in 1958 when outbreaks occurred in monkey colonies kept for research, Monkeypox has since become a topic of global concern due to its ability to jump from animal reservoirs to human hosts, leading to outbreaks beyond its endemic regions in Africa.
The clinical presentation of Monkeypox in humans is characterized by a range of symptoms including fever, swollen lymph nodes, exhaustion, chills, back pain, and a distinctive rash that progresses through several stages before forming a crust that eventually falls off. While these symptoms are well documented, less attention has been given to the neurological manifestations of the virus. Recent studies and sporadic case reports have highlighted the potential for MPXV to invade the central nervous system (CNS), leading to a variety of neurological complications. This article aims to provide a comprehensive analysis of the neuroinvasive properties of the Monkeypox virus, reviewing the existing literature and presenting current evidence from both human and animal studies.
Historical and Geographical Context of Monkeypox
The story of Monkeypox began in 1958, with the virus’s discovery in captive monkeys in a laboratory in Denmark. It wasn’t until 1970, however, that the first human case was documented in a 9-year-old boy from the Democratic Republic of Congo. Since then, the virus has primarily been reported in Central and West African countries, where it is considered endemic. The primary reservoirs for MPXV are wild animals, particularly rodents and primates, with transmission to humans occurring through direct contact with infected animals’ bodily fluids, bites, scratches, or the consumption of bushmeat.
There are two distinct clades of the Monkeypox virus: the Central African (Congo Basin) clade and the West African clade. The Central African clade is associated with more severe disease and higher mortality rates. Between 1970 and 1986, over 400 cases were reported in Central and West Africa, predominantly in the tropical rainforest regions where human interaction with wild animals is more common. The virus remained relatively contained within these regions until 2003, when the first outbreak outside of Africa occurred in the United States. This outbreak was traced back to imported Gambian pouched rats, which had transmitted the virus to prairie dogs, popular pets at the time. This event underscored the virus’s potential for global spread, facilitated by international trade and travel.
In recent years, Monkeypox has made headlines again, with outbreaks reported in countries where the virus was previously unknown. The most notable of these was in 2022, when a British traveler returning from Nigeria became the first confirmed case in the United Kingdom. By June 22, 2022, the virus had spread to 50 countries, with over 3,413 confirmed cases reported. This global spread has raised alarms among public health officials and highlighted the need for a deeper understanding of the virus’s pathophysiology, including its potential to cause neurological disease.
Virology and Pathogenesis of Monkeypox
Monkeypox virus is a large, enveloped virus with a linear double-stranded DNA genome. It replicates in the cytoplasm of infected cells, relying on the host cell’s machinery to carry out the process of translation. The virus is resistant to a range of environmental conditions, including heat and cold, making it a resilient pathogen capable of surviving in various environments. MPXV virions are ovoid or brick-shaped, measuring approximately 200 by 250 nanometers in size, with a lipoprotein outer membrane that is visible under electron microscopy.
The virus infects host cells through the interaction of viral proteins with host glycosaminoglycans, triggering endocytosis and entry into the cell. Once inside, the virus undergoes a complex replication cycle, producing both intracellular mature virus (IMV) and extracellular enveloped virus (EEV), https://debuglies.com/2022/11/04/mutations-in-monkeypox-escape-drugs-and-vaccines/
Transmission of MPXV occurs through two primary routes: zoonotic transmission from animals to humans, and human-to-human transmission. Zoonotic transmission is typically associated with direct contact with the bodily fluids of infected animals, as well as through bites or scratches. Human-to-human transmission, which has become more prominent in recent outbreaks, occurs through close contact with respiratory droplets, contaminated materials, or direct contact with the lesions of an infected person. This mode of transmission is particularly concerning in healthcare settings and among close contacts, including sexual partners.
| Concept | Simple Explanation | Relevance |
|---|---|---|
| Monkeypox Virus (MPXV) | A virus that causes monkeypox, a disease similar to smallpox, which can spread from animals to humans and between humans. | Understanding MPXV is crucial for recognizing how it causes disease, its symptoms, and the potential for outbreaks, especially in areas where it was previously unknown. |
| Zoonotic Transmission | The process by which a disease or virus spreads from animals to humans. This can occur through direct contact with an infected animal, bites, scratches, or consuming infected animals. | Knowing how zoonotic transmission occurs helps in identifying the sources of infections and implementing measures to prevent initial outbreaks from animal reservoirs. |
| Human-to-Human Transmission | The way a disease spreads from one person to another, usually through close contact, respiratory droplets, or touching contaminated surfaces. | Understanding human-to-human transmission is key to controlling the spread of the virus, especially during outbreaks, to prevent widespread infection. |
| Neurological Manifestations | Symptoms that affect the brain and nervous system, such as headaches, confusion, seizures, and other mental or physical impairments during monkeypox infection. | Recognizing neurological symptoms is important for diagnosing severe cases early and providing appropriate medical treatment to prevent long-term damage. |
| Central Nervous System (CNS) | The part of the body consisting of the brain and spinal cord, responsible for most functions of the body and mind. | The CNS’s involvement in monkeypox indicates a more severe infection, necessitating immediate medical attention and highlighting the virus’s potential for causing serious health issues. |
| Neuroinvasive Properties | The ability of the monkeypox virus to enter and affect the brain and nervous system, leading to potentially severe neurological complications. | Understanding these properties can help in developing treatments and preventive measures to protect the brain from viral infections, reducing the risk of serious outcomes. |
| Olfactory Epithelium Route | A possible way for the virus to enter the brain through the nasal passages and olfactory (smell) system. | Knowing this route of infection helps in identifying early symptoms related to smell and preventing the virus from reaching the brain through targeted interventions. |
| Infected Monocytes/Macrophages | Immune cells that might carry the virus through the bloodstream to the brain, acting as a pathway for CNS invasion. | This understanding could lead to new treatment strategies that target these immune cells to prevent the virus from reaching and damaging the brain. |
| Public Health Implications | The broader effects of the virus on society, including the need for surveillance, prevention strategies, and healthcare preparedness. | Addressing public health implications is essential for controlling outbreaks, ensuring that healthcare systems are prepared, and minimizing the overall impact on populations. |
Neurological Manifestations of Monkeypox
While the general symptoms of Monkeypox, such as fever, rash, and lymphadenopathy, are well recognized, the virus’s impact on the nervous system has received less attention. However, emerging evidence suggests that MPXV can indeed invade the central nervous system, leading to a range of neurological symptoms. These can range from mild and nonspecific symptoms such as headaches and myalgia to more severe manifestations like encephalitis and seizures.
For instance, a severe case reported in the United States involved a patient who presented with headache, myalgia, and fatigue before progressing to more severe neurological symptoms including confusion and seizure. MRI scans revealed hyperintensities in the thalamus, brainstem, and right posterior parietal cortex, indicative of mixed cytotoxic and vasogenic brain edema. Another report from the Midwestern United States described a family cluster of MPXV, where one member developed severe encephalitis requiring hospitalization, while others experienced milder symptoms.
In Nigeria, a cross-sectional study of confirmed MPXV cases in Bayelsa State documented a variety of neurological complications, including headache, myalgia, photophobia, and pain. These reports, although scattered, suggest that the neurological manifestations of MPXV may be more common than previously thought, particularly in severe cases.
Neuroinvasive Potential of Monkeypox Virus
The neuroinvasive potential of the Monkeypox virus has been demonstrated in several animal studies, although human data remain limited. In ground squirrels, intranasal and intraperitoneal administration of MPXV has been shown to result in viral penetration into the brain, with high viral titers detected in brain tissues. Similar findings have been reported in other rodent models, including prairie dogs and rope squirrels, where MPXV DNA was detected in brain tissues following infection.
The exact mechanisms by which MPXV invades the CNS are not fully understood, but animal studies have provided some clues. One proposed route is through the olfactory epithelium, where the virus may enter the CNS directly from the nasal cavity. In ground squirrels, intranasal inoculation of the Congo Basin strain of MPXV led to significant viral replication in the nasal septum mucosa and brain tissue. Another potential route is through infected monocytes and macrophages, which may transport the virus across the blood-brain barrier. Studies in macaques have shown that MPXV antigens can be detected in circulating monocytes following intravenous injection of the virus, suggesting a hematogenous route of CNS invasion.
Public Health Implications and Future Research Directions
The potential for MPXV to cause neurological disease raises significant public health concerns, particularly in light of the virus’s increasing geographic spread and the lack of widespread immunity in populations outside of Africa. The neurological complications associated with MPXV, though currently underreported, may contribute to increased morbidity and mortality, especially in vulnerable populations.
There is an urgent need for more research to better understand the neuroinvasive properties of MPXV and the full spectrum of its neurological manifestations. This includes detailed epidemiological studies to determine the incidence and prevalence of neurological symptoms in MPXV-infected individuals, as well as experimental studies to elucidate the mechanisms of CNS invasion.
In addition, public health strategies should focus on early detection and treatment of neurological symptoms in MPXV patients, as well as preventive measures to reduce the risk of transmission. This may include enhanced surveillance for MPXV in regions outside of Africa, improved diagnostic tools for early detection of CNS involvement, and the development of targeted therapies to mitigate the impact of neurological disease.
In conclusion, the Monkeypox virus, once considered a rare zoonotic pathogen confined to remote regions of Africa, has emerged as a global public health threat with the potential for significant neurological complications. While much is known about the virus’s general pathogenesis and clinical presentation, its neuroinvasive properties remain poorly understood and warrant further investigation. The evidence presented in this article underscores the need for heightened awareness of the neurological manifestations of MPXV and the importance of continued research to better understand and address the public health implications of this emerging virus.
resource : https://link.springer.com/article/10.1007/s00415-022-11339-w
