Monkeypox, like smallpox Smallpox Smallpox is a highly contagious disease caused by the smallpox virus, an orthopoxvirus. Case fatality rate is about 30%. Natural infection has been eradicated. The main concern for outbreaks... read more , is a member of the Orthopoxvirus group. There are 2 distinct clades (groups of similar organisms descended from a common ancestor) of monkeypox: the West African clade and the Congo Basin clade. Despite its name, nonhuman primates are not monkeypox virus reservoirs. Although the reservoir is unknown, the leading candidates are small rodents (eg, squirrels) in the rain forests of Africa, mostly in western and central Africa. In November 2022, the World Health Organization introduced the name “mpox” to replace "monkeypox" (see WHO recommends new name for monkeypox disease).
Historically, human disease was mainly limited to sporadic cases and occasional epidemics, mainly in Africa. Most reported cases have been in the Democratic Republic of the Congo. Since 2016, confirmed cases have also been reported in Sierra Leone, Liberia, Central African Republic, Republic of the Congo, and Nigeria. A dramatic increase in incidence in Africa since 2000 is thought to be due to the cessation of smallpox vaccination in 1980; people who have received smallpox vaccine, even > 25 years prior, are at reduced risk of monkeypox. Cases of monkeypox in Africa are also increasing because people are encroaching more and more on the habitats of animals that carry the virus.
Prior to 2022, cases outside of Africa were directly linked to travel to western and central Africa or animals imported from the region. A notable outbreak of monkeypox occurred in the US in 2003, when infected rodents imported as pets from Africa spread the virus to pet prairie dogs, which then infected people in the Midwest. The outbreak involved 37 confirmed and 10 probable cases in 6 states, but there were no deaths (1 References Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more ).
Since May 2022, cases of monkeypox have been reported in approximately 70 countries where the disease is not endemic. Sustained person-to-person transmission outside of Africa has been demonstrated. The World Health Organization (WHO) declared the 2022 monkeypox outbreak a public health emergency of international concern (see WHO: Monkeypox Outbreak 2022). The majority of confirmed cases in nonendemic countries are in Europe and North America (see Centers for Disease Control and Prevention [CDC]: 2022 Monkeypox Outbreak Global Map). Over 29,000 cases have been reported in the US as of November 2022 (see CDC: 2022 US Map & Case Count). All cases associated with the 2022 global outbreak have been the West African clade. Cases have been reported primarily in men who have sex with men, but monkeypox should be considered in anyone who presents with a rash consistent with monkeypox (2 References Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more , 3 References Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more ).
In animal-to-person transmission, monkeypox is probably transmitted via body fluids, including salivary or respiratory droplets or contact with wound exudate. This can occur through bites or scratches from an animal or through preparation and consumption of infected animal meat.
Person-to-person transmission occurs through prolonged close contact. Routes of transmission include respiratory droplets via prolonged face-to-face or intimate physical contact, direct contact with infectious lesions or other bodily fluids, and fomites via contact with clothing or linens contaminated with lesion crusts or bodily fluids. Maternal-fetal transmission can occur via the placenta. It is currently unknown whether transmission can occur through semen or vaginal fluids. In the 2022 outbreak, many cases appear due to transmission during sexual or intimate encounters, but this is likely through direct contact with infectious lesions or respiratory secretions.
The incubation period is 1 to 2 weeks but can be as long as 3 weeks. People are infectious from the time symptoms start until all lesions have crusted and scabs have fallen off to reveal healthy skin. This typically takes 2 to 4 weeks.
Based on a transmission study in Africa, the overall secondary attack rate following contact with a known human source is 3%, and attack rates up to 50% have been reported in people living with a monkeypox-infected person (4 References Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more ). Transmission in hospital settings has been documented in an endemic setting. One case of transmission to a healthcare worker has been reported (5 References Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more ). Case fatality rate is ≤ 10% with the Congo Basin clade, but is < 1% with the West African clade.
1. Reynolds MG, Yorita KL, Kuehnert MJ, et al: Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis 194(6):773-80, 2006. doi: 10.1086/505880. Epub 2006 Aug 8. PMID: 16941343.
2. Centers for Disease Control and Prevention (CDC): Newsroom release: CDC and health partners responding to monkeypox case in the U.S, May 2022. Accessed July 26, 2022.
3. CDC: Case Definitions for Use in the 2022 Monkeypox Response. Accessed July 26, 2022.
4. Nolen LD, Osadebe L, Katomba J, et al: Extended human-to-human transmission during a monkeypox outbreak in the Democratic Republic of the Congo. Emerg Infect Dis 22 (6):1014–1021, 2016. doi: 10.3201/eid2206.150579
5. Zachary KC, Shenoy ES: Monkeypox transmission following exposure in healthcare facilities in nonendemic settings: Low risk but limited literature. Infect Control Hosp Epidemiol 43(7):920-924, 2022. doi: 10.1017/ice.2022.152. Epub 2022 Jun 9. PMID: 35676244; PMCID: PMC9272466.
Symptoms and Signs of Monkeypox
Clinically, monkeypox is similar to smallpox. A prodrome of fever, headache, and malaise is followed by a rash that progresses from macules and papules to firm, deep-seated vesicles or pustules that umbilicate, scab, and fall off over time. Lymphadenopathy occurs in monkeypox but not in smallpox.
However, atypical clinical presentations have been reported in the 2022 global outbreak; therefore, diagnosis may be delayed. In the 2022 outbreak, rashes are often reported to have started in the genital, perianal, or oral regions and do not always disseminate or progress through the typical stages. Pain at lesion sites, specifically proctitis or oral pain, may be the presenting complaint. Systemic prodromal symptoms may also be mild, absent, or appear concurrent with rash. Secondary bacterial infection of the skin and lungs may occur.
Clinical differentiation of monkeypox from smallpox Smallpox Smallpox is a highly contagious disease caused by the smallpox virus, an orthopoxvirus. Case fatality rate is about 30%. Natural infection has been eradicated. The main concern for outbreaks... read more and herpesviruses such as chickenpox Chickenpox Chickenpox is an acute, systemic, usually childhood infection caused by the varicella-zoster virus (human herpesvirus type 3). It usually begins with mild constitutional symptoms that are followed... read more or herpes simplex virus (HSV) Herpes Simplex Virus (HSV) Infections Herpes simplex viruses (human herpesviruses types 1 and 2) commonly cause recurrent infection affecting the skin, mouth, lips, eyes, and genitals. Common severe infections include encephalitis... read more may be difficult. Additionally, the diagnosis of HSV or another sexually transmitted infection Overview of Sexually Transmitted Infections Sexually transmitted infection (STI) refers to infection with a pathogen that is transmitted through blood, semen, vaginal fluids, or other body fluids during oral, anal, or genital sex with... read more does not exclude coinfection with monkeypox.
Diagnosis of Monkeypox
Polymerase chain reaction (PCR)
Diagnosis of monkeypox is by culture, polymerase chain reaction (PCR), immunohistochemistry, or electron microscopy, depending on which tests are available.
PCR assays using skin lesions (roof or fluid from vesicles and pustules and/or dry crusts) are the optimal sample. Blood PCR is limited by the short duration of viremia and is not recommended. In the US, PCR testing is available through public health laboratories and commercial laboratories.
Testing should be considered in patients with clinically compatible lesions and an epidemiologic risk factor as well as any patient with a characteristic lesion (deep-seated vesicle or pustule with central umbilication). (See also CDC: Case Definitions for Use in the 2022 Monkeypox Response.)
Treatment of Monkeypox
Most patients with monkeypox have mild, self-limited disease. This is particularly true for the West African clade responsible for the current global outbreak. Treatment is supportive with analgesics, fluids, and wound care.
Patients with severe disease, complications, or who are at risk for severe disease should be considered for antiviral treatment. This includes patients with hemorrhagic or confluent lesions, mucosal or genital involvement, or other complications requiring hospitalization; immunocompromised, pediatric, pregnant or breastfeeding patients; and patients with active exfoliative skin conditions. There is no proven, safe treatment specifically for monkeypox virus infection. However, the following treatment options are available:
The antiviral drug tecovirimat: Approved by the US Food and Drug Administration [FDA] for the treatment of smallpox—available in oral and IV formulations from the CDC via an Emergency Access Investigational New Drug (IND) protocol for the primary or early empiric treatment of monkeypox in all ages; Approved for smallpox and monkeypox in the European Union
The antiviral drugs cidofovir or brincidofovir (CMX001)
Vaccinia immune globulin (IV)
All of these drugs have activity against monkeypox in vitro and in experimental models, but there are few data to guide choice of treatment; a case series of 7 patients reported use of tecovirimat and brincidofovir (1 References Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more ). Tecovirimat is being used in some health care systems in the US in the 2022 outbreak. (See also CDC: Information for Healthcare Providers on Obtaining and Using TPOXX [Tecovirimat] for Treatment of Monkeypox and CDC: Monkeypox: Treatment Information for Healthcare Professionals.)
1. Adler H, Gould S, Hine P, et al: Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis 22(8):1153-1162, 2022. doi: 10.1016/S1473-3099(22)00228-6. Epub 2022 May 24. Erratum in: Lancet Infect Dis 22(7):e177, 2022.
Prevention of Monkeypox
Past observational data from Africa suggests that the smallpox vaccine Prevention Smallpox is a highly contagious disease caused by the smallpox virus, an orthopoxvirus. Case fatality rate is about 30%. Natural infection has been eradicated. The main concern for outbreaks... read more is at least 85% effective in preventing monkeypox, because monkeypox virus is closely related to the virus that causes smallpox (1 Prevention reference Monkeypox is caused by the monkeypox virus, an orthopoxvirus structurally related to the smallpox virus. Patients present with a vesicular or pustular rash that may be painful and often... read more ). However, previous smallpox vaccination does not always provide lifelong immunity but likely reduces illness severity. Two smallpox vaccines may be used for the prevention of monkeypox disease: JYNNEOS and ACAM2000 (see CDC: Monkeypox and Smallpox Vaccine Guidance).
The JYNNEOS vaccine is a live but weakened (attenuated) vaccinia virus that does not reproduce in the person who receives it. It is indicated for the prevention of monkeypox (and smallpox) in adults 18 years of age and older who are at high risk of monkeypox (or smallpox). JYNNEOS may also be offered to people at high risk of social exposure to monkeypox in the setting of local outbreaks (see CDC: Monkeypox Vaccination Basics; Who Should Get Vaccinated?). The vaccine is given as a series of 2 injections under the skin given 4 weeks apart. Vaccination with JYNNEOS may be an alternative for people who cannot receive ACAM2000, such as those who have a weakened immune system (see below list). However, people who have a weakened immune system may have a diminished response to the JYNNEOS vaccine. Limited data on the effectiveness of the JYNNEOS vaccine in the current outbreak are becoming available. Across 32 US jurisdictions, among males aged 18 to 49 years eligible for JYNNEOS vaccination, monkeypox incidence was 14 times as high among unvaccinated males compared with those who had received a first vaccine dose ≥ 14 days earlier (see CDC: Rates of Monkeypox Cases by Vaccination Status).
The ACAM2000 vaccine contains live vaccinia virus, which is related to the smallpox virus and provides cross-immunity to the monkeypox and smallpox viruses. It is indicated for people who are at high risk of monkeypox (or smallpox). ACAM2000 is given by rapidly jabbing a small area 15 times with a specially designed needle that has been dipped in the vaccine. This is considered one dose. Then the vaccine site is covered with a dressing to prevent the vaccina virus from spreading to other body sites or to other people. Vaccination is considered successful if a small blister develops about 7 days later. If it does not appear, people are given another dose.
Vaccination with ACAM2000 is dangerous and not recommended for some people, especially those with the following risk factors:
Weakened immune system (such as those who have AIDS or who take medications that suppress the immune system)
Skin disorders (particularly atopic dermatitis [eczema])
Age under 1 year
The Advisory Committee on Immunization Practices (ACIP) recommends that people at risk of occupational exposure to orthopoxviruses receive either the JYNNEOS or ACAM2000 vaccine to protect against infection (see CDC: Monkeypox and Smallpox Vaccine Guidance and CDC: Monkeypox/Vaccines).
Non-hospitalized patients with monkeypox should
Isolate at home until the lesions have resolved and scabs have fallen off and a fresh layer of intact skin has formed
Avoid direct physical contact with other people and animals
Not share potentially contaminated items, such as bed linens, towels, clothing, drinking glasses, or eating utensils, and should clean and disinfect commonly touched surfaces and items
Wear a mask if close contact with others in the home is necessary
Infection control measures in the hospital include having patients in a private room with the door closed. Special air handling is not required unless procedures likely to spread infectious oral secretions are performed (eg, intubation, extubation). Activities that may result in dried materials being distributed in the air or on surfaces (eg, use of fans, shaking of dirty linens) should be avoided. Appropriate personal protective equipment (PPE) includes gown, gloves, N95 level mask (or equivalent), and eye protection. EPA-registered hospital-grade disinfectants with an emerging viral pathogen claim should be used for standard disinfection. For patients with the West African clade, waste may be handled according to usual guidelines for infectious medical waste. For patients with the Congo Basin clade, medical waste is classified as Category A under the US Department of Transportation (DOT) Hazardous Materials Regulations and should be managed accordingly (see CDC: Infection Prevention and Control of Monkeypox in Healthcare Settings).
All healthcare personnel caring for patients with monkeypox should monitor for symptoms at least twice daily for 21 days from their last encounter. People with high-risk exposures (see CDC: Monitoring People Who Have Been Exposed) should be offered postexposure prophylaxis via vaccination with JYNNEOS or ACAM2000. Vaccination should ideally occur within 4 days of exposure but can be effective up to 14 days after exposure (see CDC: Monkeypox and Smallpox Vaccine Guidance).
1. Jezek Z, Grab B, Szczeniowski MV, et al: Human monkeypox: secondary attack rates. Bull World Health Organ 66(4):465-70, 1988. PMID: 2844429; PMCID: PMC2491159.
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Drugs Mentioned In This Article
|Drug Name||Select Trade|
vaccinia immune globulin