Monkeypox virus, also known as MPOX, was first identified in monkeys shipped from Singapore to Denmark in 1958^[1]. First case of monkeypox in humans was reported in the Republic of the Congo in 1970^[2]. Monkeypox virus is a member of orthopoxvirus genus (family Poxviridae)^[3]. It can be transmitted from animal to animal, animal to human, and human to human. There is little evidence on mother-to-child transmission^[4].

Monkeypox virus was first identified in monkeys shipped from Singapore to Denmark in 1958^[1]. First case of monkeypox in humans was reported in a hospitalized child in the Republic of the Congo in 1970^[2]. In the following years, monkeypox virus emerged and cases were recorded in 11 African countries. Until the late 1980s, more than 400 cases were recorded^[5]. In the early 1990s, the number of reported cases dramatically declined to notably zero cases between 1993 and 1995^[6]. In 1996, large number of cases were suspected in an outbreak in Democratic Republic of Congo but only small number of cases were laboratory confirmed^[7].

In 2003, 47 confirmed and probable cases of monkeypox were in the United States. In the following years, there has been cases of monkeypox recorded periodically in non-endemic regions, predominately in the United Kingdom and one in Singapore. All of these cases were imported from endemic regions. In May 2022, case clusters of monkeypox were traced around the world over a short period of time. As of May 22, 2022, a total of 109 cases were recorded and 87 suspected around the world. On June 2, 2022, 780 cases of monkeypox were identified or reported to the World Health Organization^[8]. As of June 15, 2022, a total of 2103 laboratory confirmed cases, including one death, have been reported to World Health Organization^[9].

Monkeypox virus is a member of orthopoxvirus genus (family Poxviridae)^[3]. The monkeypox virus genome consists of linear double-stranded DNA that multiplies in the cytoplasm of infected cell^[10]. It has two genetic clades: the west African clade and the central African (Congo Basin) clade^[11]. Possible routes of transmission are animal-to-animal, animal-to-human, and human-to-human. Virus is transmitted via direct contact with body fluids or lesions of infection person or animal, direct contact with contaminated materials such as clothing, and via respiratory secretions^{_CDC_Online_Newsroom_|_CDC-12|[12]}. The role of vaginal fluids and semen in the transmission of the virus is still being investigated^{_Monkeypox_|_Poxvirus_|_CDC-13|[13]}.

Animal-to-human transmission: The virus can be acquired through daily exposure to an infected animal or complex exposure to an infected animal (e.g. invasive bite or scratch that breaks the skin). Also through direct contact with lesions or bodily fluids of an infected animal.

Human-to-human transmission: The virus can be acquired through close physical contact with infected person, direct contact with lesions, bodily fluids, or respiratory secretions of an infected person, direct contact with contaminated materials^{_CDC_Online_Newsroom_|_CDC-12|[12]}, or via placenta from mother to fetus^[14][15][4].

• Smallpox
• Chickenpox
• Scabies
• Syphilis
• Bacterial skin infections
• Drug-associated allergy

Precise prevalence and incidence are difficult to establish due to paucity of reporting in previous outbreaks. The median age in the the 1970s and 1980s was 4 and 5 years. In the 2000s and 2010s, the median age of monkeypox infection increased to 10 and 21 years. In May 2022, the average median age of monkeypox infections was 37 years.

Risk factors for contacting monkeypox virus include close physical contact with infected person or animal (including direct contact with lesions, bodily fluids, and respiratory secretions), direct contact with contaminated materials such as towels^[16][17], eating undercooked meat^[18], and complex exposures to infected animal (e.g., invasive bite or scratch that breaks the skin)^[19].

Monkeypox is usually a self-limited disease with the symptoms resolving within 2 to 4 weeks. Complications are rare. They include secondary bacterial infection such as pneumonia, sepsis, encephalitis, corneal inflammation of the eyes^[20][21][22], and conjunctivitis^[23].

The significant information in the patient’s history include recent travel to endemic area of monkeypox or possible contact with infected person, animal, or contaminated material. Initial symptoms fever, chills, lymphadenopathy, headache, myalgia, followed by skin rash of multiple lesions that develop and evolve at the same time. The evolvement of the lesions progresses as follows: macular (1−2 days), papular (1−2 days), vesicular (1−2 days), pustular (5-7 days), lastly scab (7-14 days)^{_Monkeypox_|_Poxvirus_|_CDC-24|[24]}.

Depending on the stage of the disease, physical findings may include low-grade fever, enlarged lymph nodes (submental, submandibular, cervical, inguinal), and skin rash with typical progression: Macular (1-2 days), papular (1-2 days), vesicular (1-2 days), pustular (5-7 days), scabs (7-14 days)^{_Monkeypox_|_Poxvirus_|_CDC-24|[24]}.

Polymerase chain reaction (PCR) is the preferred test to confirm monkeypox virus (MPXV) given its sensitivity and accuracy. Samples should be obtained from skin lesions, precisely, the roof or fluid from vesicles and pustules, and dry crusts^[25]. PCR blood tests are usually inconclusive because the does not live long in the blood^[14].

There are no EKG findings associated with monkeypox.

Ultrasound may be helpful to assess the fetus well-being in pregnant women with laboratory confirmed monkeypox^[15].

Currently, there is no proven, safe treatment for monkeypox. To contain the outbreak, the CDC advises using smallpox vaccine, cidofovir, ST-246, and vaccinia immune globulin. Vaccines are not available to public as for now but in an event of larger outbreak, the CDC will establish guidelines on who to receive the vaccine.

Surgery is not indicated for monkeypox. Monkeypox is usually a self-limiting disease with symptoms lasting from two to four weeks^[14].

The Advisory Committee on Immunization Practices recommends ACAM2000 or JYNNEOS as pre-exposure prophylaxis to individuals at risk of exposure to monkeypox on basis of an occupational assessment^[26].

The CDC recommends proper hand hygiene with soap and water or alcohol-based hand sanitizers after contact with infected animals or humans. Avoid contact with animals that can act as a reservoir for the virus, e.g. rodents. Avoid close contact with lesions, bodily fluids, or respiratory droplets, or contaminated materials such as bedding or towels. Personal protective equipment (PPE) is essential for healthcare workers when handling patients. Isolate infected patients to reduce spread^{_Monkeypox_|_Poxvirus_|_CDC-27|[27]}.

Monkeypox virus was first identified in monkeys shipped from Singapore to Denmark in 1958^[1]. First case of monkeypox in humans was reported in a hospitalized child in the Republic of the Congo in 1970^[2]. After 1970, monkeypox virus emerged and cases were recorded in 11 African countries. Until the late 1980s, more than 400 cases were recorded^[3]. In the early 1990s, the number of reported cases dramatically declined to notably zero cases between 1993 and 1995^[4]. In 1996, large number of cases were suspected in an outbreak in Democratic Republic of Congo but only small number of cases were laboratory confirmed^[5].

In 2003, 47 cases of monkeypox were confirmed in the United States. In the following years, there has been cases of monkeypox recorded periodically in non-endemic regions, predominately in the United Kingdom and one in Singapore. All of these cases were imported from endemic regions. In May 2022, case clusters of monkeypox were traced around the world over a short period of time. As of May 22, 2022, a total of 109 cases were recorded and 87 suspected around the world. On June 2, 2022, 780 cases of monkeypox were identified or reported to the World Health Organization^[6]. As of June 15, 2022, a total of 2103 laboratory confirmed cases, including one death, have been reported to World Health Organization^[7]. As of October 19, 2022, a total of 74,785 cases were confirmed globally, including 32 deaths^{_Monkeypox_|_Poxvirus_|_CDC-8|[8]}.

• The clinical expression of monkeypox was first described in 1958. Poxlike disease was observed in cynomolgus (Macaca cynomolgus) monkeys that were shipped from Singapore to a research facility in Copenhagen, Denmark. The virus was isolated and identified as monkeypox virus^[1].
• First case of monkeypox in humans was reported on September 1, 1970. A 9-month-old child was suspected of having smallpox and admitted to Basankusu Hospital in Democratic Republic of the Congo. Specimen was collected from patient and sent the World Health Organization Smallpox Reference Center in Moscow, Russia. The specimen revealed a virus similar to, if not identical with, monkeypox virus^[2].
• Since 1970, monkeypox virus emerged and cases were recorded in 11 African countries: Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Cote d’Ivoire, Liberia, Nigeria, the Republic of the Congo, Sierra Leone and South Sudan. Until 1990, more than 400 cases were recorded.
• Between 1970 and 1979, the World Health Organization (WHO) confirmed 54 cases^[3][9].
• Between 1981 and 1986, the WHO conducted an intensive active surveillance, confirming 338 cases and 33 deaths^[10][11].
• Number of reported cases declined after ending the Monkeypox surveillance program. In Cameroon, Gabon and the Democratic Republic of the Congo, 6 cases were reported in 1987, one in 1990, 5 in 1991 and one in 1992.
• Between 1993 and 1995, no cases of monkeypox were reported to the WHO^[4].
• Between 1996 and 1997, 511 cases were suspected in an outbreak in Democratic Republic of Congo although only small number were laboratory confirmed^[5].

As of June 7, 2003, cases of suspected monkeypox in the United States had been reported among residents of Wisconsin (18), northern Illinois (10), and northwestern Indiana (1). The disease stemmed from a giant Gambian pouch rat imported by a pet shop in Texas and is believed to have infected domesticated prairie dogs, which were then distributed by other outlets in the Midwest. Electron microscopy and serologic studies were used to confirm that the disease was human monkeypox.

By June 9, CDC officials said the number of suspected or confirmed cases was 22 in Wisconsin, 10 in Indiana, and five in Illinois.

As of June 11, a total of 54 persons with suspected monkeypox had been reported in Wisconsin (20), Illinois (10), Indiana (23), and New Jersey (1). Monkeypox had been confirmed by laboratory tests in nine persons. At least 14 of the people with suspected monkeypox had been hospitalized for their illness; there have been no deaths related to the outbreak. The number of cases and states involved in the outbreak will likely change as the investigation continues.

As of July 8, 2003, a total of 71 cases of monkeypox have been reported to CDC from Wisconsin (39), Indiana (16), Illinois (12), Missouri (two), Kansas (one), and Ohio (one); these include 35 cases laboratory-confirmed at CDC and 36 suspect and probable cases under investigation by state and local health departments^[12].

The onset of illness among patients in the United States began in early May 2003. Patients typically experienced a prodrome consisting of fever, headaches, myalgias, chills, and drenching sweats. Roughly one-third of patients had nonproductive cough. This prodromal phase was followed 1-10 days later by the development of a papular rash that typically progressed through stages of vesiculation, pustulation, umbilication, and crusting. In some patients, early lesions have become ulcerated. Rash distribution and lesions have occurred on head, trunk, and extremities; many of the patients had initial and satellite lesions on palms and soles and extremities. Rashes were generalized in some patients. After onset of the rash, patients have generally manifested rash lesions in different stages. All patients reported direct or close contact with prairie dogs, most of which were sick. Illness in prairie dogs was frequently reported as beginning with a blepharoconjunctivitis, progressing to presence of nodular lesions in some cases. Some prairie dogs have died from the illness, while others reportedly recovered.

There has been cases of monkeypox recorded periodically over the past few years in non-endemic regions. All of these cases were traced back to travel history to endemic areas or healthcare providers involved in the treatment^{[13][14][15][16]}.

In May 2022, case clusters of monkeypox were traced around the world over a short period of time. Unlike previous cases, there was no association to travel history to endemic areas of monkeypox such as Central Africa and West Africa.

Patient zero is believed to be the confirmed case on May 4, 2022 of a British resident returning back to England from Nigeria^[17]. Additional cases were identified in the UK that were neither travel-associated nor had a connection to previous cases^[18]. On May 18th, 2022, 5 cases were confirmed in Portugal^[19], 7 in Spain^[20], and 1 in the United States^{_Monkeypox_|_Poxvirus_|_CDC-21|[21]}. As of May 22, 2022, a total of 109 cases were recorded and 87 suspected around the world. On June 2, 2022, 780 cases of monkeypox were identified or reported to the World Health Organization^[6]. As of June 15, 2022, a total of 2103 laboratory confirmed cases, including one death, have been reported to World Health Organization^[7]. Although monkeypox is not known as a sexually transmitted disease, most of the cases were identified among men who have sex with men^[22]. A surge in the number of cases was observed by August 7, 2022, including 11 reported deaths^[23]. Undiagnosed cases of monkeypox and lack of testing and quarantining of individuals reporting symptoms may have contributed to this surge.^[24]. As of August 17, 2022, a total of 39,434 cases were reported worldwide^{_Monkeypox_|_Poxvirus_|_CDC-8|[8]}, including 19,429 reported Europe^[25], and 387 in locations that have historically reported monkeypox^{_Monkeypox_|_Poxvirus_|_CDC-8|[8]}. As of October 19, 2022, a total of 74,785 cases were confirmed globally, including 32 deaths^{_Monkeypox_|_Poxvirus_|_CDC-8|[8]}.

Precise prevalence and incidence are difficult to establish due to paucity of reporting in previous outbreaks. The median age of patients infected with monkeypox in the 1970s and 1980s was 4 and 5 years, respectively. In the 2000s and 2010s, the median age of persons infected with monkeypox increased to 10 and 21 years. In May 2022, the average median age of monkeypox infections was 37 years.

In the Democratic Republic of the Congo, the incidence rate of monkeypox was 0.64 per 100,000 persons in 2001. Between 2005 and 2007, the average annual cumulative incidence of confirmed monkeypox was 0.53 per 100,000 persons^[1]. This rate has increased to 2.82 in 100,000 persons in 2013^{[2]_PLOS_Neglected_Tropical_Diseases-3|[3]}.

In the Central African Republic, the attack rate of suspected or confirmed monkeypox was 20 per 100,000 persons in a 2015 outbreak^[4], and 500 per 100,000 persons in the 2016 outbreak^[5].

The annual case fatality rate of monkeypox disease is approximately 8.7 %^[6].

The case fatality rate for the Central African clade is (10.6%) significantly higher than that of the West African clade (3.6%), according to pooled data from 28 peer-reviewed articles and 10 reports^[6][7].

• Cases detected in the 2022 outbreak in the US and Europe have been associated with the West African clade of monkeypox virus^[8].

• United States
  • In 2003, the median age for the 82 patients for whom age data were available was 28 years^[9].
  • In May 2022, the mean age for 17 reported cases of monkeypox was 40 years ^{_MMWR-10|[10]}.
  • In September 2022, median age for the 21,008 reported cases was 34 years (range: <1 year to 89 years)^{_Monkeypox_|_Poxvirus_|_CDC-11|[11]}.

• Africa:
  • In the 1970s and 1980s, the median age of monkeypox infection was 4 and 5 years.
  • In the 2000s and 2010s, the median age of monkeypox infection was 10 and 21 years.
• Portugal: In May 2022, the median age of monkeypox infection was 33 years^{_Ongoing_monkeypox_virus_outbreak,_Portugal,_29_April_to_23_May_2022-12|[12]}.
• Ireland: In May 2022, the median age of monkeypox infection was 37 years ^[13].
• United Kingdon: In May 2022, the median age of monkeypox infection was 38 years old^[14].

Men are more commonly affected with monkeypox than women. In previous outbreaks, men represented more than 50% of cases^[6]. In the 2022 outbreak, men accounted for the majority of the cases^[15].

Risk factors for contracting monkeypox virus include close physical contact with infected person or animal (including direct contact with lesions, bodily fluids, and respiratory secretions), direct contact with contaminated materials such as towels^[1][2], eating undercooked meat^[3], and complex exposures to an infected animal (e.g., invasive bite or scratch that breaks the skin)^[4].

• Close physical contact with an infected person or animal^[1][2].

• Direct contact with lesions, bodily fluids, or respiratory secretions of an infected person or animal^{_Monkeypox_|_Poxvirus_|_CDC-5|[5][3][6]}.

• Direct contact with contaminated materials such as animal cages, blankets, or towels^{_Monkeypox_|_Poxvirus_|_CDC-5|[5][4]}.

• Consumption of undercooked meat of infected animals^[1].

• Daily exposure or complex exposure to an infected animal. “Complex” exposures (e.g., invasive bite or scratch that breaks the skin) were associated with shorter incubation periods, pronounced signs of systemic illness, and hospitalizations^[3][4].

Currently, there are no established screening programs or guidelines for monkeypox in the Americas, Europe, or MENA “Middle East and North Africa” region.

• Monkeypox has been periodically identified in very small numbers in non-endemic regions.
• As of June 13, 2022, no screening measures were recommended in the Americas, Europe, or MENA “Middle East and North Africa” region.
• The Department of Disease Control in Thailand took precautionary measures, screening travelers arriving into Thailand international airports as a response to the 2022 global outbreak. The screening targets arrivals from countries where monkeypox cases have been reported^[1].
• The Department of Health in the Philippines establishes a monitoring and surveillance program in light of the global outbreak.
• The Center for Health Protection in Hong Kong established a preparedness and response plan for monkeypox that includes three-tier response level system with each level representing a graded risk of monkeypox affecting Hong Kong and its health impact on the community^[2].

Monkeypox is a double-stranded DNA virus that belongs to family Poxviridae^[1][2]. It has two genetic clades: the West African clade and the Central African (Congo Basin) clade^[3].

Animal-to-human: The virus can be acquired through daily exposure to an infected animal or complex exposure to an infected animal (e.g. invasive bite or scratch that breaks the skin). It can also be acquired through direct contact with lesions or bodily fluids of an infected animal. Human-to-human: The virus can be acquired through close physical contact with infected person, direct contact with lesions, bodily fluids, or respiratory secretions of an infected person^{_Monkeypox_|_Poxvirus_|_CDC-4|[4]}, via placenta from mother to fetus^{[5][6][7]_NEJM-8|[8]}, or direct contact with contaminated materials^{_CDC_Online_Newsroom_|_CDC-9|[9]}.

Monkeypox is a member of orthopoxvirus genus, which is a subdivision of Chordopoxvirinae that belongs to family Poxviridae^[1]. It is a linear double-stranded DNA virus that multiplies in the cytoplasm of infected cell^[2]. The virus has two genetic clades: the West African clade and the Central African (Congo Basin) clade^[3].

Animal-to-human: The virus can be acquired through daily exposure to an infected animal or complex exposure to an infected animal (e.g. invasive bite or scratch that breaks the skin). Also through direct contact with lesions or bodily fluids of an infected animal.

Human-to-human: The virus can be acquired through close physical contact with infected person, direct contact with lesions, bodily fluids, or respiratory secretions of an infected person, or direct contact with contaminated materials ^{_CDC_Online_Newsroom_|_CDC-9|[9]}. The role of semen and vaginal fluids is being investigated^{_Monkeypox_|_Poxvirus_|_CDC-4|[4]}. Transmission from mother to fetus via placenta is possible, resulting in congenital monkeypox^{[5][6][7]_NEJM-8|[8]}.

Attending to the characteristics of its lesions, monkeypox will have to be differentiated from other diseases that cause a vesicular rash and a fever, including chickenpox, smallpox, herpes zoster and erythema multiforme.

Different rash-like conditions can be confused with monkeypox and are thus included in its differential diagnosis. The various conditions that should be differentiated from monkeypox include:^{[1][2][3][4][5][6][7]}

Monkeypox is usually a self-limited disease with the symptoms resolving within 2 to 4 weeks. Complications are rare. They include secondary bacterial infection such as pneumonia, sepsis, encephalitis, corneal inflammation of the eyes^[1][2][3], and conjunctivitis^[4].

The complications of monkeypox are rare.

• Common complications include secondary bacterial infection such as pneumonia, sepsis, encephalitis, corneal inflammation of the eyes^[1][2][3], and conjunctivitis^[4].
• Recent reported complications were painful proctitis, tonsillitis, penile edema, and skin abscesses^[5].

Uncomplicated cases resolve within 2 to 4 weeks. Complications may lead to death. Most reported deaths were among children, and HIV patients^[6][7][8].