Monkeypox · What Is It, Causes, and More

Published: May 29, 2025

Author: Anna Hernández•

Editor: Alyssa Haag•

Editor: Ian Mannarino, MD, MBA•

Editor: Kelsey LaFayette, DNP, RN

Illustrator: Jessica Reynolds, MS•

Copyeditor: David G. Walker

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What is monkeypox?

Monkeypox is a viral infectious disease that causes a febrile illness along with a characteristic skin rash and swollen lymph nodes. Monkeypox symptoms are similar to those seen in the past in individuals with smallpox, although it is clinically less severe. With the worldwide eradication of smallpox in 1980, monkeypox has recently emerged as one of the most important pox-like diseases affecting public health.

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Where does the name monkeypox come from?

The name monkeypox originates from the initial discovery of the virus in 1958 when two outbreaks of a pox-like disease occurred in colonies of monkeys kept for research. The first human case was identified in the Democratic Republic of the Congo in 1970. Since then, monkeypox has been reported in rural, rainforest regions of central and western African countries with the majority of infections occurring in the area of the Congo Basin. In 2003, the first monkeypox outbreak outside of Africa was identified in the United States. This outbreak led to over 70 monkeypox cases in the United States and was linked to human contact with infected pet prairie dogs that had been imported from Ghana.

Since 2017, Nigeria has experienced a large monkeypox outbreak with over 500 suspected cases and over 200 confirmed cases as of June 2022. Additionally, isolated cases of monkeypox have been reported in travelers from Nigeria to Israel, United Kingdom, Singapore, and the United States. In May 2022, multiple cases of monkeypox were identified in several non-endemic countries, including Portugal, Spain, United Kingdom, and other countries of the European Union as well as the United States, Canada, and Australia.

What causes monkeypox?

Monkeypox is caused by infection with the monkeypox virus, a member of the Orthopoxvirus genus of the Poxviridae family. The Orthopoxvirus genus also includes the variola virus, the causative agent of smallpox, as well as the vaccinia virus, which is used in the production of the smallpox vaccine. There are two different clades (or evolutionary groups) of monkeypox virus, including the West African clade and the Congo Basin (i.e,. Central African) clade. The Congo Basin clade causes a more severe disease course and is thought to be more contagious than the West African clade.

Monkeypox virus can be transmitted by contact with an infected person or animal, including rope squirrels, tree squirrels, Gambian pouched rats, dormice, and different species of monkeys among others. Transmission from one person to another can occur by close contact with infected skin lesions; bodily fluids; respiratory droplets; and contaminated objects, such as clothing, towels, or bedding. Transmission can also occur from mother to fetus via the placenta, which can lead to congenital monkeypox as well as during close contact with the virus during and after birth.

What are the signs and symptoms of monkeypox?

According to the Centers for Disease Control and Prevention (CDC), the incubation period of monkeypox is usually 6 to 14 days, but can range from 5 to 21 days. The first few days are characterized by a febrile illness consisting of fever, chills, intense headache, swelling of the lymph nodes (i.e., lymphadenopathy), back pain, muscle aches, and lack of energy. Within one to three days after the appearance of fever, individuals typically develop a characteristic rash. Initially, lesions consist of a flat, red base that evolves into slightly raised firm lesions. Afterwards, lesions turn into vesicles filled with yellowish fluid, which then turn to crusts that dry and eventually slough off. The number of lesions may vary from a few to several thousand. In severe cases, lesions may form together until they coalesce and large sections of skin ultimately slough off. Although lesions may appear anywhere on the body, they are typically concentrated on the face and extremities rather than the trunk. The mouth, eyes, and genitals may also be affected.

Complications of monkeypox include secondary infections, pneumonia, sepsis, encephalitis, and infection of the eye’s cornea with subsequent loss of vision. The mortality of monkeypox ranges from 0 to 10% with severe cases occurring more frequently in children and in individuals with underlying immune deficiencies.

What are the differential diagnoses for monkeypox?

Differential diagnoses involve considering various possible conditions that could be causing symptoms and then ruling out each one through use of history, clinical evaluation, diagnostic tests, and critical thinking. This process helps to narrow down the list of potential diagnoses to determine the most likely cause of the symptoms.

Differential diagnoses can be broken down into four categories: most likely, less likely, least likely, and can’t miss. Most likely diagnoses are conditions most probable based on symptoms and clinical presentation. Less likely diagnoses are not as probable but should still be considered. On the other hand, least likely diagnoses can be considered if other, more probable conditions are excluded. Finally, can’t miss diagnoses are less common but critical to promptly identify and treat as they can lead to severe consequences.

Differential diagnoses for monkeypox include:
Most likely:

Varicella: Vesicular rash in various stages of healing, often with fever and malaise.
Herpes simplex virus: Painful grouped vesicles, often localized to oral or genital areas.
Molluscum contagiosum: Umbilicated papules, more common in children or immunocompromised individuals.
Hand, foot, and mouth disease: Vesicular lesions on hands, feet, and oral mucosa, often in children.

Less likely:

Insect bites: Can cause papular or vesicular lesions with surrounding erythema.
Drug eruptions: May present with widespread rash, sometimes vesicular or bullous.

Least likely:

Syphilis (secondary): Can present with a generalized rash, including palms and soles, but usually non-vesicular.
Eczema herpeticum: Disseminated HSV infection in patients with atopic dermatitis.
Dermatitis herpetiformis: Intensely pruritic vesicles, often on extensor surfaces, associated with celiac disease.
Contact dermatitis: May cause vesicles or bullae, typically localized to area of exposure.

Can’t miss:

Disseminated herpes zoster: Especially in immunocompromised patients; widespread vesicular rash.
Severe bacterial superinfection: Can complicate monkeypox lesions, leading to cellulitis or sepsis.
Sepsis or systemic viral illness: If monkeypox is misdiagnosed and systemic symptoms worsen.

How is monkeypox diagnosed?

Diagnosis of monkeypox is suspected based on the appearance of an unexplained rash illness consistent with monkeypox, a history of contact with an infected individual or laboratory exposure, or travel history to an endemic country within 21 days of symptom onset. Differential diagnosis of monkeypox includes other febrile rashes, such as chickenpox, measles, bacterial skin infections, scabies, syphilis, and medication-associated allergies.

In cases where monkeypox is suspected, a diagnostic sample from a skin lesion may be obtained for analysis. The preferred laboratory test is a polymerase chain reaction (PCR), which detects the presence of the viral genetic material. Because orthopoxviruses are structurally similar to each other, they are serologically cross-reactive, meaning that laboratory tests that assess for antibodies against monkeypox may not be able to confirm the disease. In addition, vaccination with a vaccinia-based vaccine (e.g., anyone vaccinated with the smallpox vaccine or more recently vaccinated due to higher risk, such as orthopoxvirus laboratory personnel) may lead to false positive results.

How is monkeypox treated?

Currently, there are no specific treatments available for monkeypox infection; however, certain antivirals developed for smallpox and other viruses may be used in individuals with severe illness or increased risk of complications. According to the Centers for Disease Control and Prevention (CDC), current options for the treatment of monkeypox include antivirals tecovirimat (i.e., TPOXX), cidofovir (i.e., Vistide), brincidofovir (i.e., Tembexa), and the vaccinia immune globulin intravenous (i.e., VIGIV).

Because monkeypox virus is closely related to the virus that causes smallpox, the smallpox vaccine can protect individuals from getting monkeypox with an efficacy of up to 85%. Experts also believe that vaccination after monkeypox exposure may help prevent the disease or make it less severe. Exposure to the live smallpox vaccination leaves a sore and itchy bump that blisters and results in a permanent scar on the upper arm. Currently, the original smallpox vaccine is not available for the general public, though a more recent smallpox vaccine may be administered to certain health workers or laboratory personnel to protect them in the event of exposure to monkeypox in the workplace.

What are the most important facts to know about monkeypox?

Monkeypox is a viral infectious disease with symptoms similar to those seen with smallpox, although it is clinically less severe. It presents with a febrile illness that progresses into a characteristic skin rash and swollen lymph nodes. The evolution of lesions progresses through four stages—macular, papular, vesicular, to pustular—before scabbing over and resolving. Monkeypox is endemic to tropical rainforest areas of central and western Africa and is occasionally exported to other regions of the world, causing important public health outbreaks. Transmission to humans may occur through close contact with infected animals or persons or with objects contaminated by the virus. Currently, there is no specific treatment for monkeypox infection, though several antivirals may be used in certain extreme cases. Because monkeypox virus is closely related to the virus that causes smallpox, the smallpox vaccine can protect individuals from contracting monkeypox.

References

Elsevier. (2022, August 16). Monkeypox. Elsevier healthcare hub. https://elsevier.health/en-US/monkeypox/home

Monkeypox. (2022, May 19). In World Health Organization. Retrieved June 2, 2022, from https://www.who.int/news-room/fact-sheets/detail/monkeypox

Monkeypox and smallpox vaccine guidance. In Centers for Disease Control and Prevention. Retrieved June 2, 2022, from https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.html

Multi-country monkeypox outbreak in non-endemic countries. (2022, May 21). In World Health Organization. Retrieved June 2, 2022, from https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385

Petersen, B. W., Harms, T. J., Reynolds, M. G., & Harrison, L. H. (2016). Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses — Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. Morbidity and Mortality Weekly Report, 65(10): 257–262. DOI: 10.15585/mmwr.mm6510a2

U.S. monkeypox 2022: Situation summary. (2022). In Centers for Disease Control and Prevention. Retrieved June 2, 2022, from https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html