Monkeypox is an infectious disease caused by the monkeypox virus, a member of the orthopoxvirus genus, which also comprises the variola virus (the causative agent of smallpox), vaccinia viruses (the viruses in the smallpox vaccine), and cowpox virus. Monkeypox is a zoonotic disease, meaning it can be transmitted from animals to humans. The natural reservoirs of the virus are not fully understood, but it is known to infect a variety of animal species, including rodents and non-human primates (Shehryar et al., 2023). The disease was first discovered in laboratory monkeys in 1958, and the first human case was reported in 1970 in the Democratic Republic of Congo. Since then, monkeypox has been endemic to several Central and West African countries.
Monkeypox can be transmitted from animals to humans through bites or scratches, direct contact with an infected animal’s bodily fluids or lesions, or exposure to contaminated materials such as bedding or equipment. Human-to-human transmission can occur through respiratory droplets during prolonged face-to-face contact, as well as through direct contact with an infected person’s bodily fluids, skin lesions, or contaminated materials (A Huang et al., 2022). The incubation period for monkeypox is usually 7-14 days, but can range from 5-21 days. The illness typically begins with fever, headache, muscle aches, backache, swollen lymph nodes, chills, and exhaustion. A rash often develops within 1-3 days after the onset of fever, starting on the face and then spreading to other parts of the body. The rash goes through several stages before forming a scab, which eventually falls off. The duration of the illness is usually 2-4 weeks.
Historical Background
In 1958, the first outbreaks of monkeypox occurred in monkeys in laboratory colonies in Danmark as well as the US, in an attempt to explore African wildlife as an exotic pet market. These animals were in fact infected with monkeypox, an orthopoxvirus closely related to variola virus (the cause of smallpox). The name monkeypox in homage to the species of animal involved in the first recorded outbreak (Lu et al., 2022). It was not until 1970 that the first human case was isolated. A 9-month-old boy in the Democratic Republic of Congo became infected in the context of ongoing monkeypox outbreaks in the neighbouring Republic. The disease remained exclusively endemic to Central and West Africa for several decades after its discovery (Shehryar et al., 2023).
In the late 1990s, cases re-emerged in urban environments, likely due to deforestation and increased human-wildlife contact. In 2003, the first outbreak of monkeypox was documented in the US with 81 confirmed cases. In 2017, monkeypox infected people for the first time in Nigeria outside of the DRC (from where it has been exported to over 20 countries since 1970), with more than 400 reported cases over a 3-year period. The 2022 outbreak revealed that monkeypox can now spread on a much larger scale.
Signs and Symptoms
Monkeypox, a viral zoonotic infection, is endemic to tropical rainforest regions of central and west Africa. The disease typically manifests in two phases, including a prodrome of fever, malaise, headache, fever, or lymphadenopathy lasting 1 to 5 days, followed by a distinctive rash. The rash begins on the face and then disseminates to other regions. On the face, the rash is often concentrated on the forehead and eyebrows. Lesions are more commonly seen on the legs and arms than on the trunk. Inguinal and axillary rashes are more common than those seen in chickenpox. Lesions progress through the macular, papular, vesicular, and pustular phases, and then become crusted. Serious illness occurs more frequently with concomitant infections (for example, malaria or HIV) or in children < 8 years, particularly in those without exposure to smallpox vaccine (M Patel and V Patel, 2023).
The name “monkeypox” stems from the isolation of the virus from imported macaque monkeys in a Danish laboratory in 1958. The clinical disease was first observed in a 9-month-old male in the Democratic Republic of the Congo in 1970. This patient survived monkeypox but later died from a supervening measles infection. After this initial recognition, sporadic cases were reported in the same region. As monkeypox was first discovered in a child, it was postulated that the disease might be a childhood illness. This observation is plausible since most cases occurred in children, and the disease can be severe in children affected < 5 years. However, early cases may have gone unnoticed in adults since these would be the first generation of individuals unprotected by vaccination (A Huang et al., 2022).
Epidemiology and Global Distribution
The public health authorities in different countries should monitor cases with rashes and flu-like symptoms, even in people with no travel history to endemic areas. Countries with a low incidence should strengthen surveillance and contingency plans for possible importation of the disease from endemic countries. Multi-national companies like GSK and Bavarian Nordic, along with the Drug Controller General of India (DCGI), should provide support in containing the disease early on. The general community should be made aware about monkeypox, its symptoms and transmission, and the importance of consulting a doctor if any concerns arise.
Monkeypox is an infectious disease caused by the monkeypox virus. It was first discovered in 1958 when a mad monkey in Denmark was responsible for an outbreak of pox-like disease in laboratory monkeys. Later, in 1970, the first cases in humans were reported in the then-Zaire, Africa. The first outbreak was reported in the USA in 2003 when an infant who kept pet prairie dogs fell sick. From June to July 2022, the number of confirmed and suspected cases of monkeypox increased by 48% globally. Many new countries were affected, including India, that were previously free from monkeypox. WHO declared monkeypox as a Public Health Emergency of International Concern (PHEIC) in July 2022, urging all member countries to strengthen surveillance, report cases, and combat disease spread (Shehryar et al., 2023).
Outbreaks and Incidence Rates
Monkeypox is an infectious disease that has drawn increased attention in recent years due to numerous outbreaks and epidemiological investigations in non-endemic areas. The recent outbreaks detected in Europe, North America, Oceanian countries, and other areas not previously endemic for monkeypox are alarming, especially due to the significantly low population immunity against the virus (Shehryar et al., 2023). There is increasing curiosity regarding the issue of monkeypox, including the virus characteristics, transmissibility, clinical features, and population susceptible to infection.
The name “monkeypox” itself stems from the virus’s isolation from Macaca fascicularis in 1958, intended to be used for polio vaccine research. While the virus was first discovered in laboratory monkeys (hence the name), the known natural reservoir has been the correctly mimicked rodent species. C. en and a host of the genus Heliothis were identified as reservoir hosts of monkeypox virus, with both being known habitats of other Orthopoxviruses. Unlike in Africa, where squirrels, rodents, and prairie dogs were implicated in folk narratives of human infection, monkeypox caused outbreaks in a cohort of exotic African animals in the United States. Multiple species—including the swabbed macaques, sooty mangabeys, grey’s and white-nosed capuchin monkeys, marmosa, and African dormouse—were all suspected to play a role in the outbreak (A Huang et al., 2022). Additionally, because C. aethiops and Plasmodium reside in the same rodent family as prairie dogs, African rodents could further be implicated in the outbreak in 2003. Most recently, an African squirrel (E. rufulus) was found to be seropositive to the virus by an ELISA assay with a novel monoclonal antibody. Understanding the outbreaks and incidence rates in specific regions can help identify areas at high risk of outbreaks like concentrations of imported animals, aviaries, or other animal markets. The epidemiological study of monkeypox can aid surveillance and reporting systems, including logs of animal trade, schedules for animal importation, and wildlife surveillance programs in non-endemic countries.
Transmission and Reservoir Hosts
Monkeypox is caused by monkeypox virus; it is a zoonotic disease caused by the primate isolation of the orthopox virus genus. The dark-pigmented lesions mainly affect children, differing from smallpox infections. The clinical history, epidemiological findings, and diagnoses of the first US case and the recent outbreak are discussed. The signs and symptoms expressed during the first week of the cycle are pock-like vesicle formations, where severe head and back pains occur. This was accompanied by multiple pock-like lesions on the face, torso, beads, and palms, combined with close contact with MDVC monkeypox. To study this, animals were used, but no acquired or patent infections were observed, suggesting higher neurovirulence in humans. The clinical features and spread of the 2003 outbreak are presented.
Recently described, mature virion-sized enveloped oval structures are seen instead of the classic dumbbell-shaped. EPMV was isolated from the cerebellum of a rhesus monkey evaluated for als-like syndrome. Once either the cell or organ culture is infected with poxvirus, it produces large intracellular inclusions and becomes swollen, dying within a few days, leading to a cytopathic or lytic effect. Virus particle exo- or cellular release occurs through lysis and subsequently infects new cells, where the life cycle continues. The viral genome is made of part double-stranded DNA of about 200 to 300 kb, containing more than 150 open reading frames (ORFs). Transcription of early genes occurs within the viral factories and is coupled with the generation of intracytoplasmic viral envelopes, either in the form of envelopes inducing cellular swelling or cytoplasmic bodies. When found in the brain, it has been motor neuron-associated. A concentration of 102.66 pfu of EPMV was produced; MCB254 clones were intramedully (IM) infected; and controls were IM infected with BJK30-vaccinia virus. A central role for CD4+ T cells in the protective measures is suggested and is related to the occurrence of strong-mdidelayed graanuloma-forming hypersensitivity responses.
Human-to-Human Transmission
Zoonotic diseases have long posed a global challenge, triggering new pandemics that significantly affect public health systems. Many of the world’s diseases have similar origins, often taken on by people in close contact with animals. The diseases can either be mild or severe; some can be transmitted between populations, mutating to form totally new strains. The neglected viruses have a serious potential resurgence danger through climate/environmental/human behavioral changes. One of those viruses is monkeypox, an Orthopoxvirus first described in monkeys in 1958 and now slowly re-emerging in the human population following several decades of quiescence. The recent 2022 global outbreak of monkeypox in regions of the world that have never reported previous human cases and the largely already exhausted specialized smallpox vaccines raises enormous concerns about the behavior of poxviruses that have been neglected for long periods of time.
The Monkeypox virus can be transmitted from animals to humans or humans to humans by direct contact with infected lesions, bodily fluids or by contacting objects or surfaces contaminated with the virus. Monkeypox virus can survive for long periods in scabs or shed from lesions (Krishna et al., 2024). Understanding the mechanisms and pathways of human-to-human transmission is pivotal (A Huang et al., 2022). Asymptomatic transmission likely occurs metapopulation analysis indicated that there were eight distinct clades of this virus on earth with much divergence between the two main clades, suggesting distinct diseases with a variety of human population effects. Models would need to be designed with pressure considerations to simulate advancing disease outbreaks, moving from population to population as new susceptible individuals are brought into contact with the virus. These models can aid in further understanding previously neglected diseases such as Monkeypox.
Preventive Measures
Vaccination against monkeypox is one of the most essential considerations that emerged in the early 2022 outbreaks. Post-exposure vaccination within four days of exposure is currently recommended for at-risk close contacts and health care workers, to prevent this debilitating disease. In September 2022, the U.S. government allocated the JYNNEOS vaccine to states. Safe clonal-vaccinia-derived live-attenuated vaccine, VE (ACAM2000) is E.cn and V and E of smallpox and monkeypox Poxvirus. V is a large and complex (>200 kb) DNA virus with a linear dsDNA genome (Shehryar et al., 2023).
As a preventative treatment, it is used for non-severe orthopoxvirus infections and intended for children >1 y and immune compromised people to avoid associated adverse effects. Nonreplicating vaccinia-vectored MPXV-gene-based recombinant vaccine, N as a viable alternative to Poxvirus vaccines. First-generation vaccines are based on live, replicating vaccinia virus strains such as Dryvax and ACAM2000. poxvirus vaccines have been shown to be more effective than no vaccines towards preventing disease, but their efficacy is still uncertain. Those vaccines posed significant health risks to infants, immunosuppressed patients and others with contraindications. Second generation live virus, safer vaccines were developed, such as IMVAMUNE, LC16m8 and MVA-BCG. Live vector-based Vaccination against monkeypox viral disease is one of the most essential considerations that emerged in the early 2022 outbreaks (A Huang et al., 2022).
Vaccination and Treatment Options
Focusing on vaccination and treatment options, these provide insights into a critical aspect of preventive measures against monkeypox. These insights garner more knowledge for guiding vaccination campaigns and treatment protocols. This knowledge is fundamental for the preparation of vaccination campaigns, development of treatment protocols, and effective allocation of medical resources, which ultimately helps in the mitigation of the disease’s impact and prevention of its spread (Shehryar et al., 2023). Currently, there are four vaccines available for monkeypox or smallpox: ACAM2000, JYNNEOSTM, IMVAMUNE/IMVASKA, and LC16. These vaccines differ in several aspects, and both ACAM2000 and JYNNEOSTM proved efficacious in the event of outbreaks (A Huang et al., 2022). There are two FDA-approved treatments against orthopoxvirus infections: Tecovirimat (Tpoxx), an antiviral agent, and Vaccinia immune globulin intravenous (VIGIV), a polyclonal vaccinia virus-neutralizing immunoglobulin. Tecovirimat was designated as an orphan drug for the treatment of smallpox in 2016, per the 2018 FDA’s Animal Rule. Since then, monkeypox virus has been recognized as a suitable surrogate pathogen, especially in nonhuman primate studies. Owing to the persistence of anti-orthopox virus antibodies (anti-OPV) in at-risk populations, the prophylactic and therapeutic benefits of anti-OPVs were also explored.