The monkeypox virus, like its cousin the variola virus (the causative agent of smallpox), is a DNA virus of the genus Orthopoxvirus. Monkeypox was first noted in the late 1950s when outbreaks of a “pox-like disease” were observed in monkeys housed in research facilities, hence the name “monkeypox” ( Despite the name, the zoonotic reservoir for the monkeypox virus has not been determined.

According to the Centers for Disease Control & Prevention (CDC) website on monkeypox, the primary symptoms of monkeypox are skin rashes. The rashes may occur anywhere but are most common on the area of contact with infected individuals, such as the hands, mouth, face, genitalia, or anus ( Additional systemic symptoms include backache, chills, cough, exhaustion, fever, muscle aches, nasal congestion, sore throat, and swollen lymph nodes.

As noted by the CDC, monkeypox transmission occurs through “personal, often skin-to-skin contact” ( Specifically, the CDC notes that monkeypox is transmitted by direct contact with rashes, sores, or exudates of people infected with monkeypox. Infection can also occur via contact with the “respiratory secretions” or contact with infected fomites.

Most cases of monkeypox have been documented in Africa, where monkeypox is endemic in rodents. The first documented case of human monkeypox was in the Basankusu Territory of the Democratic Republic of the Congo in 1970. Cases outside of Africa were “linked to international travel to countries where the disease commonly occurs or through imported animals” (Bull World Health Organ 1972;46:593-7).

“The current ongoing outbreak of monkeypox has largely remained within the male gay and bisexual communities. However, as with HIV decades ago, there is no reason to expect a transmissible disease to remain within this population.”

Monkeypox briefly made headlines in 2003 following an outbreak in six U.S. states ( The outbreak was the result of a shipment of exotic animals from West Africa (Ghana) to a facility in Texas. It is thought that the virus was first transmitted to other captive animals such as prairie dogs, and from there to humans.

The 2003 outbreak comprised 47 cases: 37 confirmed cases and 10 probable cases (J Infect Dis 2006;194:773-80). Patient symptoms and disease course depended on the type of exposure. Systemic illness was observed in 49% of the patients who were bitten or scratched by an infected animal. Two-thirds of these patients required hospitalization. Systemic illness was only observed in 17% of those who were simply exposed to an infected animal, and only 10% of these patients required hospitalization.

This year, monkeypox is again in the headlines with almost 22,000 cases in the U.S. and 57,000 cases globally. Several of these have been associated with superspreader events (

The prior African cases of monkeypox were separated into different clades, Congo Basin (clade I) and West African (clades IIa and IIb)( The current monkeypox outbreak most closely resembles the West African clade, which is typically less severe than the Congo Basin clade, which can have a mortality rate of 10%.

A recent report provided a detailed summary of 528 cases at 43 treatment centers in 16 different countries between April 27 and June 24, 2022 (N Engl J Med 2022;387:679-91). The median age of the patients was 38 years, 98% were male and gay or bisexual, and three-fourths were white. More than 40% of the cases had prior HIV infection. Almost all patients (95%) presented with a rash. Seventy-three percent also reported anogenital lesions. The most common systemic disease features were fever (62%), lymphadenopathy (56%), lethargy (41%), muscle aches (31%), and headache (27%).

Nearly 30% of the patients tested also had “concomitant sexually transmitted infections.” For the patients having a documented exposure, the incubation period ranged from three to 20 days (median: seven days). Of the 32 patients who had seminal fluid analyzed, monkeypox viral DNA was detected in 29. Only 13% of the cases required hospitalization, primarily for pain management. No deaths were recorded in these cases.

In a recent letter to the New England Journal of Medicine, Lane and Fauci note that “the emerging epidemiologic pattern of these cases bears a striking resemblance to the early cases of HIV/AIDS. Men who identified as homosexual or bisexual accounted for 98% of cases” (N Engl J Med 2022;387:749-50).

There are currently two vaccines available for monkeypox: a licensed replication-deficient vaccinia vaccine (JYNNEOS) and a live vaccinia virus vaccine available under the Food and Drug Administration (FDA) Expanded Access-Investigational New Drug mechanism (N Engl J Med 2022;387:679-91). Two drugs are also available: the orthopox-targeting tecovirimat and the DNA virus antiviral brincidofovir. These two treatments are available through the “Animal Rule” (“efficacy is established based on adequate and well-controlled studies in animal models of the human disease or condition”)(


A recent New England Journal of Medicine article discussed the use of tecovirimat to treat monkeypox (N Engl J Med 2022;387:579-81). Unfortunately, the trial of tecovirimat in the Democratic Republic of the Congo treated infections caused by a different clade than the current outbreak. As a result, the presentation of monkeypox was very different from the current outbreak. The NIH is now planning “a U.S.-based randomized clinical trial to assess the safety and efficacy of tecovirimat for the treatment of monkeypox disease.” The trial will be coordinated with the AIDS Clinical Trials Group, taking advantage of their experience with the at-risk population.

An article in the Journal of the American Medical Association from the University of California at Davis described a small uncontrolled trial evaluating oral tecovirimat in 25 patients with confirmed monkeypox infections (JAMA August 2022). Tecovirimat was well tolerated. Complete resolution of lesions was noted in 40% of patients by day seven and in more than 90% of patients by day 21. The data appear promising, but without a control group the study is uninterpretable regarding tecovirimat efficacy.

An article from The Lancet described a patient with monkeypox treated with oral tecovirimat (Lancet 2022;4:e8). The patient was also HIV-infected with “metastatic Kaposi sarcoma, secondary syphilis, and hypertension.” The patient received 600 mg tecovirimat orally BID for two weeks without evidence of adverse events. His lesions quickly resolved.

A recent New England Journal of Medicine article by authors from the CDC and FDA discussed the potential for switching from the standard subcutaneous injection to an intradermal delivery of the JYNNEOS vaccine (N Engl J Med August 2022;387:579-81). The authors explain that the intradermal space is an “anatomically favorable site for immune stimulation, enriched in a heterogeneous population of dendritic cells, macrophages, and monocytes that endow this tissue with a potent capacity to detect and respond robustly to immunologic stimuli, including those present in vaccines.” The authors recommend that people who are at highest risk for contracting monkeypox should receive both shots of the JYNNEOS vaccine sequence. They also suggest that vaccine manufacturers should evaluate their products in clinical trials utilizing intradermal dosing “in order to expand our understanding of this operationally attractive option.”

The current ongoing outbreak of monkeypox has largely remained within the male gay and bisexual communities. However, as with HIV decades ago, there is no reason to expect a transmissible disease to remain within this population. In their letter to the New England Journal of Medicine (N Engl J Med 2022;387:749-50), Lane and Fauci revisited Fauci’s accurate prediction about HIV/AIDS in 1982 (!): “Any assumption that it will remain restricted to a particular segment of our society is truly an assumption without a scientific basis”(Ann Intern Med 1982;96:777-9). Based on this prescient observation from 40 years ago, Lane and Fauci suggest that “additional detailed epidemiologic and observational cohort studies, serosurveys, and ongoing surveillance for new cases are of critical importance.”