Introduction

Mpox, previously known as monkeypox, is an infectious disease caused by the monkeypox virus, belonging to the genus Orthopoxvirus within the Poxviridae family. Initially observed in macaque monkeys, it is a zoonotic disease, thereby transmittable through animals, including small mammals such as rodents, and human-to-human contact. The first human case of mpox emerged in a young patient from the Democratic Republic of the Congo in 1970.

Over the subsequent decades, more human mpox cases were identified in western and central Africa, marking the disease as endemic. However, there has been a recent increase in mpox cases beyond endemic countries, with the UK registering the first re-emergent case in 2022.¹ According to the World Health Organisation’s latest data as of December 2023, 117 countries globally have reported 93,030 confirmed mpox cases.²

The symptomatology of mpox reflects other viral infections, resembling smallpox, measles, and chickenpox. Typical symptoms include swelling of the lymph nodes (lymphadenopathy) and rash-like lesions. Complications, however, may arise, ranging from bacterial infections and vision loss to pneumonia, encephalitis, and, in severe cases, death.³

Causes and transmission

Two main strains of the mpox virus have been identified: clade I, or Congo Basin (central African clade), considered more lethal, and clade II, or West African clade, a less severe variant. Upon recent analyses of 2022 outbreaks, a third clade, clade IIb has surfaced.¹ Despite the connotation of the term ‘monkeypox’, which suggests where the virus was initially observed, its source remains elusive.⁴

Mpox can spread from infected animals who can transmit it to other animals and humans.Animal-to-human transmission may occur through a bite or scratch from an infected animal, or contact with their lesions, bodily fluids, and contaminated objects.⁵

Human-to-human transmission can occur through the inhalation of respiratory droplets, direct contact with the patient’s skin, mouth sores, or contact with contaminated objects. Additionally, sexual contact, oral or penetrative, vaginal or anal, may serve as a mode of transmission. The transmissibility of the virus through semen or vaginal fluids remains uncertain, and thus it is not officially recognised as a sexually transmitted infection.⁶

Symptoms and progression

The incubation period, the period from virus exposure to symptom onset, varies from several days to a few weeks, during which no symptomatology is present. Specific symptoms associated with mpox include:^5,7

• Fever
• Headache
• Muscle aches
• Sore throat
• Low energy
• Lymphadenopathy
• Rash

Systemic symptoms typically precede skin rash, although reverse instances have also been documented. The rash unfolds through distinct stages, initiating as flat, red spots (macules), which then evolve into pumps (papules), clear fluid-filled blisters (vesicles) and then pustules. The latter pus-filled blisters eventually dry, form crusts, and fall off. Lesions may manifest across the body, in the face, mouth, eyes, trunk, limbs, genital, and anal regions, lasting 2-4 weeks. Contagion typically persists from the initial appearance of the rash until crust detachment, although evidence of asymptomatic individuals transmitting the virus has occurred.⁷

Symptoms appearance and duration fluctuate among individuals and are often managed through supportive care and medications. However, newborns, children, pregnant individuals, and those with compromised immune systems face an elevated risk of developing severe mpox and presenting potentially life-threatening complications.⁷

Potential complications

Dermatologic complications

The typical rash observed in most mpox patients may, in some cases, give rise to more severe complications. The shedding of crusts can lead to scar formation, which can persist for years. The skin damage caused by mpox stands as a predominant cause of secondary bacterial skin infections, the most prevalent complication of mpox.⁸

People living with HIV and immunocompromised individuals are at a higher risk of developing these serious secondary infection.⁹ Moreover, rashes in the vaginal and anal areas have been associated with intense pain and secondary bacterial cellulitis. Sepsis, due to the extensive number of skin lesions, also poses a life-threatening complication of mpox. Additionally, further damage to the oral and ocular cavities have been reported.⁸

Respiratory complications

Respiratory symptoms, such as cough, shortness of breath, chest pain, and difficulty breathing, manifest in around 12%-78% of mpox cases.¹⁰ Acute tonsillitis is also considered a common symptom linked to mpox. Nonetheless, one of the most severe pulmonary complications attributed to mpx is bronchopneumonia. Unvaccinated and/or immunocompromised individuals are at higher risk of developing respiratory symptoms.

Data from the recent outbreak of mpox in the US marked an 11% incidence of pneumonia among individuals living with HIV.¹⁰ Coinfections with influenza viruses, SARS-CoV-2, or other respiratory viral pathogens can exacerbate pulmonary symptoms, augmenting the susceptibility to secondary bacterial infections.¹⁰ Acute respiratory distress syndrome has also been reported as a potential respiratory complication linked to mpox.^11,12

Neurological complications

Headache, fatigue, and myalgia are some of the most common neurological symptoms of mpox. However, rarer, yet severe, complications have been described. The precise mechanisms underlying the neuroinvasive properties of the monkeypox virus are yet to be understood, emphasising the need for further studies, particularly investigations of the long-term neurological effects of mpox.¹³

Encephalitis and seizures are identified as the most infrequent yet serious complications of mpox and have been observed sporadically, notably in unvaccinated neonates and people living with HIV. In case of neurological signs in viral infection patients specific exams are recommended, including cerebrospinal fluid analysis for detecting the virus.¹⁴

Ocular complications

Ocular manifestations linked to mpox have been reported in specific cases across outbreaks. Conjunctivitis, photophobia, pain, and lesions are specific eye symptoms that patients with mpox may exhibit, with the former two ranking as the most prevalent ophthalmic symptoms. The noteworthy variability in the occurrence rates of these symptoms between past and current outbreaks underscores the necessity of in-depth investigation of these trends.

Furthermore, more severe but rare events such as keratitis, corneal ulcers, vision loss in one or both eyes, and impaired vision have been documented. A potential secondary bacterial infection could also be a causative agent for further complications in mpox patients. The most severe ocular complications tend to prevail among unvaccinated individuals thereby highlighting the need to familiarise individuals at high-risk groups with prevention methods.^15,16

Cardiovascular complications

Diverse cardiac manifestations of varying types and severity have surfaced in cases of mpox viral infection. Patients presenting symptoms like chest pain, shortness of breath, and palpitations have been documented during the mpox outbreaks, prompting a closer examination of cardiovascular abnormalities. Myocarditis, pericarditis, congestive heart failure, arrhythmias, and vascular deficits, including irregularities in blood flow and thrombosis, have all been reported during the 2022 mpox outbreak.

The exact mechanisms by which the monkeypox virus can damage the heart muscle and the extent of the damage, are still under research. These complications could significantly undermine the quality of life for patients and even result in severe outcomes. Therefore, proper diagnosis and continuous monitoring of patients with these symptoms are crucial for effectively managing the progression of the disease.¹⁷

Prevention and future perspectives

The recent global outbreak of mpox poses new challenges, urging scientists to conduct detailed examinations of this viral infection, and establishing clear management guidelines for healthcare professionals to prevent the rare but, in some cases, severe and fatal complications. Public awareness is also one of the most potent weapons in eradicating such viral infections.⁵

Markedly, the recent mpox outbreak indicated a higher prevalence among men who have sex with men (97.4% of cases), and bisexual individuals.⁴ Nevertheless, anyone in close contact with a symptomatic individual with mpox or having multiple sex partners faces a potential risk of contracting the infection. Raising awareness and educating people in high-risk groups are paramount steps for limiting the spread of this infection and protecting vulnerable populations.⁵

Severe complications are uncommon and mpox typically only requires quarantine and supportive care for managing mild symptoms such as headache and pain. However, children, pregnant women, and immunocompromised individuals, particularly those with uncontrolled or advanced HIV, are more susceptible to severe complications. Prompt management of mpox in the early stages is pivotal for preventing the occurrence of potential complications. Those at high risk of infection are recommended to avoid contact with infected people, consult their healthcare provider for personalised advice, and consider vaccination.⁵

Summary

In summary, mpox is a relatively rare yet contagious viral infection induced by the monkeypox virus. Two original strains of the virus were identified in central and west Africa, until recent confirmed cases were reported in the 2022 outbreaks in multiple non-endemic countries. The epidemiologic rates indicate that mpox is mostly but not solely observed among men who have sex with men. However, anyone can get infected by close or intimate contact with infected individuals, touching contaminated objects, or exposure to infected animals. Common symptoms of mpox include rash and swelling of the lymph nodes, along with fever and flu-like symptoms.

Currently, no approved treatment plan exists, with quarantine, supportive care, and pain control medications being sufficient for most cases. Certain populations, however, including immunocompromised individuals have a heightened risk of severe illness and complications. Sepsis, pneumonia, encephalitis, vision loss, myocarditis, and death are some of the most extreme complications of mpox. Therefore, enlightenment and implementation of protective measures in both healthcare providers and high-risk individuals are imperative for managing this current outbreak. If you suspect you have mpox or you belong to a high-risk group, consult your physician to receive proper information and guidance on how to protect yourself and others.