Monkeypox virus is a zoonotic Orthopoxvirus and a possible biothreat agent that causes human disease with varying morbidity and mortality. Today, monkeypox is considered the most important orthopoxvirus infection in human beings since the eradication of smallpox. It is a potentially severe illness that begins with a high fever, followed by the development of a characteristic rash.

Clinical presentation

After exposure to the virus and infection, there is an incubation period that varies between 6 and 14 days, followed by a prodromal period of about 1-3 days before the appearance of the typical maculopapular rash. During this prodrome phase the affected individual can experience fever, malaise and swollen lymph nodes, with possible occurrence of other symptoms such as sweats, headache, backache, shortness of breath, sore throat and cough.

Lymph node enlargement can arise in the submandibular, cervical or inguinal regions, and such lymphadenopathy is important when distinguishing mokeypox from smallpox, as it is not a common feature in the latter disease. It is observed in approximately 90% of all human monkeypox infections, and the enlarged lymph nodes are tender, firm and sometimes even painful.

After the prodrome period, typical maculopapular rash develops with mean diameter of the skin lesions from 0.5 to 1 centimeter. The number of lesions can range from a few to thousands, and during a period of 2-4 weeks they progress from macules to papules, vesicles, pustules and finally a crusting phase characterized by umbilication, scabbing, and desquamation.

The lesions most often affect oral mucous membranes (in 70% of cases) and genitalia (in 30% of cases), but can also affect eyelids and the cornea. Extracutaneous manifestations, such as secondary skin or soft-tissue infections, have been observed in 19% of unvaccinated monkeypox patients. Encephalitis can also arise, but in less than 1% of all cases.

Therapy and management

Currently, there are no licensed antiviral drugs for the treatment of monkeypox. Several agent are promising as antiviral therapeutics against the viruses from the genus Orthopoxvirus – and among them monkeypox as well. By inhibiting viral DNA polymerase, cidofovir shows antiviral activity against a myriad of viruses, although it has not been used to manage orthopoxvirus infection in humans.

There is insufficient data to assess whether severe monkeypox infection could benefit from the treatment with immune globulin. That kind of treatment may be considered as a prophylactic in exposed individuals with severe immunodeficiency of T-cell function where smallpox vaccination is contraindicated.

Vaccination with vaccinia virus (i.e. the smallpox vaccine) results in a significant amount of protection against infection with monkey pox. Still, the vaccine is currently not used in monkeypox-endemic areas due to the concerns about severe adverse events in an immunocompromised population. Furthermore, the eradication of monkeypox is not feasible because of the existence of an animal reservoir.

The Centers for Disease Control and Prevention recommends pre-exposure vaccination for individuals investigating animal or human monkeypox cases, people with the direct contact with animals that could carry the pathogen, health care workers taking care of the patients with monkeypox and laboratory workers who handle specimens that may contain this virus.

Close contact with patients during the disease outbreak represents the most significant risk factor for monkeypox virus infection. As specific treatment and vaccine are lacking, raising awareness about the risk factors and proper education about preventive measures are the only efficient ways to reduce the burden of this disease.

Further Reading

• All Monkeypox Content
• What is Monkeypox?
• Monkeypox Epidemiology
• Monkeypox 2003 U.S. Outbreak

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.