Monkeypox (Mpox)

Practice Essentials

In 1970, when smallpox was nearly eradicated, a previously unrecognized orthopoxvirus named monkeypox (mpox) was identified in humans. The first known human case occurred in the Equateur province of Zaire (now known as the Democratic Republic of Congo [DRC]) when a 9-year-old boy developed a smallpoxlike illness, which was eventually confirmed as human monkeypox by the World Health Organization. [1] Retrospectively, similar cases occurring in 1970-1971 from the Ivory Coast, Liberia, Nigeria, and Sierra Leone were attributed to monkeypox infection.

Monkeypox was limited to the rain forests of central and western Africa until 2003, when the first cases in the Western Hemisphere were reported. In late spring 2003, multiple persons were identified in the midwestern United States who had developed fever, rash, respiratory symptoms, and lymphadenopathy following exposure to ill pet prairie dogs (Cynomys species) infected with the monkeypox virus. [2]

In the most recent outbreak in 2022, the United Kingdom reported 9 cases of monkeypox in early May 2022, with the first identified case having recently traveled to Nigeria. From this adult index case, there were 2 confirmed transmissions within the patient's family, to another adult and a toddler. [3]  On May 18, 2022, the Massachusetts Department of Public Health announced a confirmed case of monkeypox in an adult male who had recently visited Canada. [4]

From 2022 to July 31, 2024, more than 100,000 confirmed cases of mpox, caused by MPXV clade I and II, were reported globally across over 120 countries, resulting in over 200 deaths, according to the WHO's report on the 2022-24 Mpox (Monkeypox) Outbreak: Global Trends.

Cases of monkeypox in the US peaked in early August 2022 with a 7-day moving average of 439. Owing to vaccination and avoidance in at-risk populations, the 7-day average of 48 cases have decreased as of October 19, 2022. 

An overwhelming, though not exclusive, number of cases in the current outbreak are among men who have sex with men. [8] While sexual transmission has not been definitively confirmed, this mode of transmission seems likely, especially given that initial lesions are often reported at sites of sexual contact. [9, 10]  

In the 2003 US outbreak, imported asymptomatic animals transmitted a nonindigenous pathogen to an indigenous susceptible animal. After an average incubation period of 12 days, the animal became ill and was capable of transmitting the pathogen to humans when in close proximity. The exact potential for human-to-human transmission and human-to-animal transmission remains unknown.

Note the image below.

Vesicular rash on the dorsal aspect of the hand. Vesicopustules are seen; some have a central umbilication.

In July 2021, a case of monkeypox was reported in Dallas, Texas in a traveler from Nigeria. [11, 12] Later, in November of that year, a second US case was confirmed in Maryland in another traveler returning from Nigeria. [11, 13]  These 2 cases represent the only reported incidents of monkeypox in the US during 2021. 

Etiology

Outbreaks in western and central Africa have been linked to exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Inhabitants of remote tropical rain forests may become infected from direct contact while capturing, slaughtering, and/or preparing these animals for food; ingestion has also been linked to infection. Consumption of such so-called "bush meat" is particularly hazardous because the flesh is often undercooked. Because of the diversity of animals eaten by local inhabitants, conclusions about the relative risk of meat sources are not known with certainty.

Prognosis

Mortality rates ranging from 1-10% have been reported in Africa, but no fatalities occurred in the United States 2003 outbreak.

History and physical examination

Monkeypox can cause a syndrome clinically similar to smallpox but overall is less infectious and less deadly.

Transmission can occur from contact with ill animals or animal reservoirs from Western Africa (eg, prairie dogs, rabbits, rats, mice, squirrels, dormice, monkeys, porcupines, gazelles). Additionally, preparing or ingesting infected animals can transmit monkeypox infection. Finally, direct cutaneous (skin-to-skin) or respiratory contact with an animal or person who is infected can transmit the infection.

The incubation period averages 12 days, ranging from 4-20 days.

In the prodromal or preeruptive stage (lasts 1-4 days prior to the onset of rash), [14]  fever is commonly the first symptom (usually 38.5-40.5°C). The febrile illness is often accompanied by chills, drenching sweats, severe headache, backache, myalgia, malaise, anorexia, prostration, pharyngitis, shortness of breath, and cough (with or without sputum). Lymphadenopathy appears within 2-3 days after the fever. In the 2003 outbreak, 47% of patients had nodes measuring several centimeters in diameter in the cervical and submental areas.

In the exanthem (eruptive) stage, most persons develop a rash within 1-10 days after the onset of fever. The rash often starts on the face and then spreads to the rest of the body. It persists for 2-4 weeks until all lesions have shed the crusts. However, in the current outbreak, painless anogenital lesions — often without a prodrome — are being observed in persons who have had close contact with an infected person or persons, including men who have sex with men. [15]

Encephalitis with immunoglobulin M (IgM) found in the cerebrospinal fluid has been reported. [16]

The most reliable clinical sign differentiating monkeypox from smallpox and chickenpox is enlarged lymph nodes, especially the submental, submandibular, cervical, and inguinal nodes. [17]

Also see Physical Examination.

Complications

Complications include pitted scars, deforming scars, secondary bacterial infection, bronchopneumonia, respiratory distress, keratitis, corneal ulceration, blindness, septicemia, and encephalitis.

Diagnostics

On November 15, 2002, the United States Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the cobas MPXV to detect monkeypox virus DNA in swabs from human monkeypox lesions in patients with suspected monkeypox cases. [18]

Refer to the information established by the US Centers for Disease Control and Prevention (CDC) at Monkeypox: Clinical Recognition.

Treatment

The disease is usually self-limited; resolution occurs in 2-4 weeks. In the African cases, the mortality rate was 1-10%, and death was related to the patients' health status and other comorbidities. Most patients died of secondary infections. No fatalities were reported in the 2003 US outbreak.

Patients often feel poorly during the febrile stage of the illness; therefore, bedrest along with supportive care may be necessary. Hospitalization may be necessary in more severe cases; a negative pressure room is preferable.

In September 2019, the US Food and Drug Administration (FDA) approved an attenuated, live, nonreplicating smallpox and mpox (monkeypox) vaccine (Jynneos) for immunization of adults at high risk for smallpox or mpox infection. [19, 20]  It also has an emergency use authorization (EUA) for use in children. 

Another poxvirus vaccine (ACAM2000) gained FDA approval for mpox in 2024.

Also see Clinical management and infection prevention and control for monkeypox: Interim rapid response guidance, 10 June 2022 from the World Health Organization (WHO).

Clinical Presentation

Physical Examination

The most reliable clinical sign differentiating monkeypox (mpox) from smallpox and chickenpox is enlarged lymph nodes, especially the submental, submandibular, cervical, and inguinal nodes. [17] Note the image below.

Lymphadenopathy in monkeypox. Large nodes in the mandibular, cervical, or inguinal region are commonly seen in monkeypox. The presence of significant lymphadenopathy helps differentiate monkeypox from smallpox and chickenpox.

The 2022 outbreak has produced atypical symptoms when compared to previous monkeypox outbreaks. [9] These symptoms may include:

• Scant or even single lesions or even the complete absence of skin lesions

• Lesions mostly confined to the genital and perianal areas, presenting with anal pain and bleeding

• Lack of prodromal symptoms, such as fever, myalgias, fatigue, and headache before the appearance of a rash

Some patients experience herald cutaneous lesions at the point of sexual contact prior to further symptoms.

Previous outbreaks

With regard to enanthema, nonspecific lesions and inflammation of the pharyngeal, conjunctival, and genital mucosae have been observed.

In the exanthema stage, within a particular body region, lesions evolve synchronously over 14-21 days, similar to the development of lesions with smallpox. However, unlike smallpox, skin lesions may appear in crops. In contrast to smallpox, the lesions do not have a strong centrifugal distribution. Lesions progress from macules to papules to vesicles and pustules; umbilication, crusting, and desquamation follow. Most lesions are 3-15 mm in diameter.

Note the image below.

Umbilicated papule on the lower part of the leg. This smaller lesion still shows the typical umbilicated morphology.

The face, the trunk, the extremities, and the scalp are involved. Lesions appear in covered and uncovered areas. Lesions may be seen on the palms and the soles. Necrosis, petechiae, and ulceration may be features. Pain is unusual, and, if it occurs, it is often associated with secondary bacterial infection. Pruritus may occur.

In patients who have been previously vaccinated against smallpox, a milder form of disease occurs. In children, the lesions may appear as nonspecific, erythematous papules that are 1-5 mm in diameter and suggestive of arthropod bite reactions. Subtle umbilication may be seen.

In the African outbreaks, 20% of unvaccinated patients developed a confluent, erythematous eruption on the face and the upper part of the trunk, which some authors have termed the septicemic rash of monkeypox. [34]

Hemorrhagic and flat forms, which can be seen with smallpox, have not been reported in patients with monkeypox. Deep pock scars can result as the lesions resolve. 

Ocular monkeypox

Ocular monkeypox is a potentially sight-threatening infection and requires urgent assessment and treatment. Signs and symptoms include vision changes, eye pain, itching, redness, swelling, and foreign body sensation. Clinicians should consider prompt initiation of treatment with systemic antiviral therapy, in addition to trifluridine ophthalmic drops in patients with ocular manifestations. 

Workup

Diagnostic Criteria

The diagnostic criteria are summarized below; refer to the current criteria established by the CDC at Monkeypox: Clinical Recognition.

Confirmed case

Meets 1 or more of the following laboratory criteria:

• Isolation of the monkeypox (mpox) virus in culture from a sample obtained from the patient

• Demonstration of the monkeypox virus on PCR in a specimen obtained from the patient

• Demonstration of the orthopox virus by electron microscopy in samples obtained from the patient in the absence of exposure to other orthopoxviruses

• Demonstration of the monkeypox virus by immunohistochemical methods in samples obtained from the patient in the absence of exposure to another orthopoxvirus

Probable case

This is contact that meets current epidemiologic criteria per the CDC. It is the occurrence of fever and vesicular-pustular rash, with the onset of the first sign or symptom at most 21 days after the last exposure, meeting the epidemiologic exposure.

Suspected case

This is contact that meets current epidemiologic criteria per the CDC. It the occurrence of fever or unexplained rash and 2 or more other signs or symptoms, with the onset of the first sign or symptom at most 21 days after exposure, meeting the epidemiologic criteria. Symptoms are as follows:

• Chills and/or sweats

• Lymphadenopathy

• Sore throat

• Cough

• Shortness of breath

• Headache

• Backache

Treatment & Management

Medical Care

The disease is usually self-limited; resolution occurs in 2-4 weeks. In the African cases, the mortality rate was 1-10%, and death was related to the patients' health status and other comorbidities. Most patients died of secondary infections. No fatalities were reported in the 2003 US outbreak.

Patients often feel poorly during the febrile stage of the illness; therefore, bedrest along with supportive care may be necessary. Hospitalization may be necessary in more severe cases; a negative pressure room is preferable.

To avoid infection of health care workers and close contacts, airborne and contact precautions should be applied. See the current CDC recommendations at Infection Prevention and Control of Monkeypox in Healthcare Settings.

Isolation must be continued until the last crust is shed. 

Also see, CDC Monkeypox resources for healthcare professionals

Antiviral Agents

Tecovirimat 

Tecovirimat (TPOXX) is approved by the FDA and is indicated for treatment of human smallpox disease caused by variola virus. Also, the CDC holds an expanded access investigational new drug (EA-IND), also called compassionate use, that allows for the use of stockpiled tecorvirimat to treat monkeypox (mpox) during an outbreak. Tecovirimat is stockpiled by the US federal Strategic National Stockpile, but administration of the drug is under an IND exemption application. [46, 47]  Preliminary data from two randomized clinical trials (PALM007 [NCT05559099] and STOMP [NCT05534984]) aimed at evaluating the effectiveness and safety of tecovirimat for treating mpox indicated that although tecovirimat is safe, it did not shorten the duration for mpox lesions to heal. Tecovirimat remains available to certain high risk patient populations

Cidofovir 

Data on the effectiveness of cidofovir in human cases of monkeypox are not available. It is indicated for cytomegalovirus in the United States. Although cidofovir has proven activity against poxviruses in in vitro  and animal studies, it is not known whether or not a patient with severe monkeypox infection will benefit from treatment. The CDC holds an EA-IND that allows for the use of stockpiled cidofovir for the treatment of orthopoxviruses (including monkeypox) in an outbreak. [46]  

Brincidofovir

Brincidofovir (Tembexa) is indicated for treatment of smallpox caused by virola virus in adults and children, including neonates. Brincidofovir is a prodrug of cidofovir diphosphate. Cidofovir diphosphate selectively inhibits orthopoxvirus DNA polymerase-mediated viral DNA synthesis. Brincidofovir may have an improved safety profile over cidofovir as severe renal toxicity or other adverse events have not been observed during treatment of cytomegalovirus infections with brincidofovir in comparison to treatment using cidofovir. The CDC is currently developing an EA-IND for to help facilitate use of brincidofovir as a treatment for monkeypox. [46, 47]  

Vaccinia immune globulin (VIG)

Data are not available on the effectiveness of VIG in treatment of monkeypox complications. Use of VIG is administered under an EA-IND for treatment of orthopoxviruses (including monkeypox) in an outbreak. It is not known whether a patient with severe monkeypox infection will benefit from VIG treatment.

VIG can be considered for prophylactic use in a monkeypox-exposed person with severe immunodeficiency in T-cell function for which smallpox vaccination following monkeypox exposure is contraindicated. [46]

Treatment of ocular monkeypox

Patients with monkeypox can experience serious ocular complications. Cases of monkeypox are mostly self-limited; however, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox may occur when the virus is introduced into the eye, most typically from autoinoculation. Ocular infection can potentially cause conjunctivitis, blepharitis, keratitis, and vision loss. 

Clinicians should consider prompt initiation of systemic antiviral therapy in addition to topical trifluridine in patients with ocular manifestations. Patients with ocular monkeypox, including those with HIV-associated immunocompromise, have experienced delays in treatment initiation, prolonged illness, hospitalization, and vision impairment The CDC emphasizes the importance of reducing the risk of ocular complications by practicing good hand hygiene and to instruct patients with ocular monkeypox to avoid touching their eyes and refrain from using contact lenses. [48]  

Medication

Medication Summary

The CDC recommends a smallpox or smallpox/monkeypox (mpox) vaccination within 2 weeks of exposure, ideally within 4 days, for exposed health care workers and household contacts of confirmed cases. Antiviral agents (ie, tecovirimat, brincidofovir, cidofovir) are possible treatment options in severe, life-threatening cases. [54, 55] These agents may be used under an expanded access investigational new drug (EA-IND) available from the CDC. [46, 47]  Additionally, vaccinia immune globulin (VIG) may be considered, but has not demonstrated efficacy as either treatment or prophylaxis. [46, 47] Smallpox preparedness research has led to the development of new antiviral agents for the treatment of orthopoxvirus infections. 

In September 2019, the FDA approved an attenuated, live, nonreplicating smallpox and mpox vaccine (Jynneos) for immunization of adults at high risk for smallpox or mpox infection. [19, 20, 47]  

The FDA granted emergency use authorization (EUA) August 9, 2022 for Jynneos to expand vaccine supply by administering a 0.1-mL intradermal dose to adults. The EUA also expands use to include children aged 18 years and younger to receive the subcutaneous 0.5-mL dose. 

Another poxvirus vaccine (ACAM2000) gained FDA approval for mpox in 2024.   

Also see further vaccine information under Medical Care

Antiviral Agents

Class Summary

Tecovirimat may be used under an expanded access investigational new drug (EA-IND) available from the CDC. Cidofovir and brincidofovir have proven activity against poxviruses in in vitro and animal studies, but only cidofovir is currently available either commercially or from the Strategic National Stockpile. 

Tecovirimat (TPOXX)

Antiviral agent indicated for treatment of human smallpox disease caused by variola virus in adults and children who weigh at least 13 kg. It is available under an expanded access (ie, compassionate use) investigational new drug protocol for adults and children (weighing at least 6 kg) for treatment of mpox. 

Cidofovir

Cidofovir is a nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Brincidofovir (Tembexa)

Indicated for treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.

Vaccine, Live Virus

Class Summary

Vaccinia vaccine promotes active immunity against the smallpox virus by inducing specific antibodies. Currently available stocks of vaccinia vaccine were derived from the vaccinia strain maintained at the New York Board of Health. Wyeth Laboratories manufactured the last batches of the vaccine (Dryvax) in the early 1980s. These batches were made by using the calf lymph method, and they were lyophilized but are no longer available.

Several attenuated vaccinia vaccine candidates are undergoing investigation, with ACAM2000 receiving FDA approval as a replacement for Dryvax. It was approved for mpox in 2024. Another vaccine (smallpox [vaccinia] and mpox vaccine, live, nonreplicating [Jynneos]) has also been approved by the FDA for immunization of adults at high risk for smallpox or mpox infection.

New, cell-derived lots of vaccinia appear to have adverse effect profiles similar to the older, calf lymph–derived lots.

Primary immunization as soon as possible after exposure or at the first sign of infection is indicated for the prevention and management of smallpox. Currently, US military personnel, US Department of Defense civilian employees, and health care professionals are recommended candidates to receive the vaccination because they will likely be at highest risk in case of a biologic attack (eg, bioterrorism).

Smallpox and mpox vaccine, live, nonreplicating (Jynneos)

August 9, 2022: Emergency use authorization (EUA) granted by FDA to expand vaccine supply by administering a 0.1-mL intradermal dose to adults. The EUA also expands use to include children aged 18 years and younger to receive the subcutaneous 0.5-mL dose.    

This vaccine is derived from a vaccinia virus, a virus that is closely related to, but less harmful than, variola and mpox viruses and can protect against both of these diseases. It is indicated for prevention of smallpox and mpox disease in adults who are at high risk for smallpox or mpox infection. It is administered as a 2-dose series administered 4 weeks apart.

Smallpox and mpox (vaccinia) vaccine, live (ACAM2000)

Indicated for active immunization for prevention of smallpox and mpox disease in individuals determined to be at high risk for infection.

Antivirals, Ophthalmic

Class Summary

Clinician should consider prompt initiation of systemic antiviral therapy in addition to topical trifluridine in patients with ocular manifestations.

Trifluridine ophthalmic (Viroptic)

Fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vacciniavirus. It is approved by the FDA for treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2. The CDC recommend off-label use for mpox ocular infections. 

References

1. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ. 1972. 46(5):593-7. [QxMD MEDLINE Link].

2. Reed KD, Melski JW, Graham MB, Regnery RL, Sotir MJ, Wegner MV, et al. The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med. 2004 Jan 22. 350(4):342-50. [QxMD MEDLINE Link].

3. Hobson G, Adamson J, Adler H, et al. Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021. Euro Surveill. 2021 Aug. 26 (32):[QxMD MEDLINE Link]. [Full Text].

4. NETEC. Outbreak Update: Mpox Outbreak in the U.S. National Emerging Special Pathogens Training and Education Center. Available at https://netec.org/2022/05/19/outbreak-update-monkeypox-outbreak-in-the-us/. May 19, 2022; Accessed: January 1, 2025.

5. 2022 Monkeypox Outbreak Global Map. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html. 2022 Oct 19; Accessed: October 19, 2022.

6. Monkeypox 2022 U.S. Map & Case Count. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html. 2022 Oct 19; Accessed: October 19, 2022.

7. Riser AP, Hanley A, Cima M, et al. Epidemiologic and Clinical Features of Mpox-Associated Deaths — United States, May 10, 2022–March 7, 2023. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/mmwr/volumes/72/wr/mm7215a5.htm. 14 April 2023; Accessed: 19 April 2023.

8. O’Shea J, Filardo TD, Morris SB, Weiser J, Petersen B, Brooks JT. Interim guidance for prevention and treatment of monkeypox in persons with HIV infection – United States. MMWR Morbidity Mortal Wkly Rep. 2022 Aug 05. [Full Text].

9. Lai CC, Hsu CK, Yen MY, et al. Monkeypox: An emerging global threat during the COVID-19 pandemic. J Microbiol Immunol Infect. 2022 Aug 5. [QxMD MEDLINE Link]. [Full Text].

10. Ghazvini K, Keikha M. Human Monkeypox resurgence 2022; a new presentation as a sexual pathogen. Ann Med Surg (Lond). 2022 Aug. 80:104267. [QxMD MEDLINE Link]. [Full Text].

11. Ellis R. Year’s Second Case of Monkeypox Discovered in Maryland. WebMD Health News. 2021 Nov 23. Available at https://www.webmd.com/a-to-z-guides/news/20211123/years-second-case-of-monkeypox-discovered-in-maryland.

12. Rao AK, Schulte J, Chen TH, et al. Monkeypox in a Traveler Returning from Nigeria - Dallas, Texas, July 2021. MMWR Morb Mortal Wkly Rep. 2022 Apr 8. 71 (14):509-516. [QxMD MEDLINE Link]. [Full Text].

13. CDC Newsroom. Imported Monkeypox case Reported in Maryland. CDC Newsroom. 2021 Nov 17. Available at https://www.cdc.gov/media/releases/2021/s1117-monkeypox.html.

14. Minhaj FS, Ogale YP, Whitehall F, et al. Monkeypox Outbreak — Nine States, May 2022. CDC - Morbidity and Mortality Weekly Report. Available at https://www.cdc.gov/mmwr/volumes/71/wr/mm7123e1.htm#T2_down. 10 June 2022; Accessed: 6 July 2022.

15. Patrocinio-Jesus R, Peruzzu F. Monkeypox Genital Lesions. N Engl J Med. 2022 Jun 15. [QxMD MEDLINE Link]. [Full Text].

16. Sejvar JJ, Chowdary Y, Schomogyi M, Stevens J, Patel J, Karem K, et al. Human monkeypox infection: a family cluster in the midwestern United States. J Infect Dis. 2004 Nov 15. 190(10):1833-40. [QxMD MEDLINE Link].

17. Osadebe L, Hughes CM, Shongo Lushima R, Kabamba J, Nguete B, Malekani J, et al. Enhancing case definitions for surveillance of human monkeypox in the Democratic Republic of Congo. PLoS Negl Trop Dis. 2017 Sep. 11 (9):e0005857. [QxMD MEDLINE Link]. [Full Text].

18. FDA NEWS RELEASE: FDA Roundup: November 15, 2022. US Food and Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-roundup-november-15-2022. 2022 Nov 15; Accessed: 2022 Nov 15.

19. Jynneos (smallpox and monkeypox vaccine, live, nonreplicating) [package insert]. Kvistgaard, Denmark: Bavarian Nordic A/S. September, 2019. Available at [Full Text].

20. US Food and Drug Administration. FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox. United States Food and Drug Administration. 2019 Sep 24. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-live-non-replicating-vaccine-prevent-smallpox-and-monkeypox.

21. Maksyutov RA, Gavrilova EV, Shchelkunov SN. Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay. J Virol Methods. 2016 Oct. 236:215-20. [QxMD MEDLINE Link].

22. Khodakevich L, Jezek Z, Kinzanzka K. Isolation of monkeypox virus from wild squirrel infected in nature. Lancet. 1986 Jan 11. 1(8472):98-9. [QxMD MEDLINE Link].

23. Hutin YJ, Williams RJ, Malfait P, Pebody R, Loparev VN, Ropp SL, et al. Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997. Emerg Infect Dis. 2001 May-Jun. 7(3):434-8. [QxMD MEDLINE Link]. [Full Text].

24. Reynolds MG, Carroll DS, Olson VA, et al. A silent enzootic of an orthopoxvirus in Ghana, West Africa: evidence for multi-species involvement in the absence of widespread human disease. Am J Trop Med Hyg. 2010 Apr. 82(4):746-54. [QxMD MEDLINE Link]. [Full Text].

25. Centers for Disease Control and Prevention. Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb Mortal Wkly Rep. 2003 Jul 11. 52(27):642-6. [QxMD MEDLINE Link]. [Full Text].

26. Karem KL, Reynolds M, Braden Z, Lou G, Bernard N, Patton J, et al. characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak. Clin Diagn Lab Immunol. 2005 Jul. 12(7):867-72. [QxMD MEDLINE Link].

27. Reynolds MG, Yorita KL, Kuehnert MJ, Davidson WB, Huhn GD, Holman RC, et al. Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis. 2006 Sep 15. 194(6):773-80. [QxMD MEDLINE Link].

28. Kalthan E, Dondo-Fongbia JP, Yambele S, Dieu-Creer LR, Zepio R, Pamatika CM. [Twelve cases of monkeypox virus outbreak in Bangassou District (Central African Republic) in December 2015]. Bull Soc Pathol Exot. 2016 Oct 25. [QxMD MEDLINE Link].

29. Durski KN, McCollum AM, Nakazawa Y, Petersen BW, Reynolds MG, Briand S, et al. Emergence of Monkeypox - West and Central Africa, 1970-2017. MMWR Morb Mortal Wkly Rep. 2018 Mar 16. 67 (10):306-310. [QxMD MEDLINE Link]. [Full Text].

30. Reynolds MG, Damon IK. Outbreaks of human monkeypox after cessation of smallpox vaccination. Trends Microbiol. 2012 Feb. 20(2):80-7. [QxMD MEDLINE Link].

31. Reynolds MG, Emerson GL, Pukuta E, Karhemere S, Muyembe JJ, Bikindou A. Detection of human monkeypox in the Republic of the Congo following intensive community education. Am J Trop Med Hyg. 2013 May. 88(5):982-5. [QxMD MEDLINE Link].

32. 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. 2016 Jun. 22 (6):1014-21. [QxMD MEDLINE Link].

33. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022. N Engl J Med. 2022 Jul 21. [QxMD MEDLINE Link]. [Full Text].

34. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human monkeypox: clinical features of 282 patients. J Infect Dis. 1987 Aug. 156(2):293-8. [QxMD MEDLINE Link].

35. Huhn GD, Bauer AM, Yorita K, Graham MB, Sejvar J, Likos A, et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005 Dec 15. 41(12):1742-51. [QxMD MEDLINE Link].

36. Jezek Z, Fenner F. Human monkeypox. Melnick JL, ed. Monographs in Virology. Basel, Switzerland: Karger. Vol 17: 1988.

37. Fine PE, Jezek Z, Grab B, Dixon H. The transmission potential of monkeypox virus in human populations. Int J Epidemiol. 1988 Sep. 17(3):643-50. [QxMD MEDLINE Link].

38. Cono J, Casey CG, Bell DM. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Recomm Rep. 2003 Feb 21. 52:1-28. [QxMD MEDLINE Link].

39. Zhao K, Wohlhueter RM, Li Y. Finishing monkeypox genomes from short reads: assembly analysis and a neural network method. BMC Genomics. 2016 Aug 31. 17 Suppl 5:497. [QxMD MEDLINE Link].

40. Likos AM, Sammons SA, Olson VA, Frace AM, Li Y, Olsen-Rasmussen M, et al. A tale of two clades: monkeypox viruses. J Gen Virol. 2005 Oct. 86:2661-72. [QxMD MEDLINE Link].

41. Hutson CL, Carroll DS, Self J, et al. Dosage comparison of Congo Basin and West African strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease. Virology. 2010 Apr 5. [QxMD MEDLINE Link].

42. US Food and Drug Administration. FDA Removes Its Portion of Interim Final Rule Banning African Rodents, Prairie Dogs and Other Animals. Available at https://www.fda.gov/animalveterinary/newsevents/cvmupdates/ucm047899.htm. Accessed: March 6, 2014.

43. Li D, Wilkins K, McCollum AM, Osadebe L, Kabamba J, Nguete B, et al. Evaluation of the GeneXpert for Human Monkeypox Diagnosis. Am J Trop Med Hyg. 2017 Feb 8. 96 (2):405-410. [QxMD MEDLINE Link]. [Full Text].

44. McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan. 58(2):260-7. [QxMD MEDLINE Link].

45. Bayer-Garner IB. Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings. J Cutan Pathol. 2005 Jan. 32(1):28-34. [QxMD MEDLINE Link].

46. [Guideline] Interim clinical guidance for the treatment of Monkeypox. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html. 2022 Jul 28; Accessed: August 10, 2022.

47. Monkeypox. National Institute of Allergy and Infectious Diseases. Available at https://www.niaid.nih.gov/diseases-conditions/monkeypox. 2022 Jun 13; Accessed: June 16, 2022.

48. Cash-Goldwasser S, Labuda SM, McCormick DW, et al. Ocular monkeypox — United States, July–September 2022. MMWR Morb Mortal Wkly Rep. October 17, 2022. [Full Text].

49. Monkeypox and smallpox vaccination guidance. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.html. 2022 June 2; Accessed: 2022 August 10.

50. Stabenow J, Buller RM, Schriewer J, West C, Sagartz JE, Parker S. A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus. J Virol. 2010 Apr. 84(8):3909-20. [QxMD MEDLINE Link]. [Full Text].

51. Hutson CL, Abel JA, Carroll DS, et al. Comparison of West African and Congo Basin monkeypox viruses in BALB/c and C57BL/6 mice. PLoS One. 2010 Jan 27. 5(1):e8912. [QxMD MEDLINE Link]. [Full Text].

52. Overton ET, Lawrence SJ, Stapleton JT, Weidenthaler H, Schmidt D, Koenen B, et al. A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS. Vaccine. 2020 Mar 4. 38 (11):2600-2607. [QxMD MEDLINE Link].

53. Rao AK, Petersen BW, Whitehill F, Razeq JH, Isaacs SN, Merchlinsky MJ, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Jun 3. 71 (22):734-742. [QxMD MEDLINE Link]. [Full Text].

54. De Clercq E. Cidofovir in the therapy and short-term prophylaxis of poxvirus infections. Trends Pharmacol Sci. 2002 Oct. 23(10):456-8. [QxMD MEDLINE Link].

55. Sherman DS, Fish DN. Cidofovir. AIDS Read. 1999 May-Jun. 9(3):215-20. [QxMD MEDLINE Link].

56. CDC. Past U.S. Cases and Outbreaks. US Centers for Disease Control and Prevention. Available at https://www.cdc.gov/mpox/outbreaks/past-us-cases/index.html. September 13, 2024; Accessed: January 1, 2025.

57. Wodi AP, Issa AN, Moser CA, Cineas S. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2025. MMWR. January 16, 2025. 74(2):30-33. [Full Text].